Accessibility / Report Error

Relationship between major depressive disorder and ACE gene I/D polymorphism in a Turkish population

Abstract

Background

Major depressive disorder (MDD) is a complex disease and a significant health problem that is prevalent across the world. Angiotensin-converting enzyme (ACE) has an important role in renin-angiotensin system (RAS) and converts inactive angiotensin I to a potent vasopressor and aldosterone-stimulating peptide angiotensin II. Levels of ACE in plasma vary according to the insertion/deletion (I/D) polymorphism of ACE gene.

Objective

The aim of the current study was to examine the influence ACE gene I/D variations on the risk of MDD.

Methods

In the present case-control study, we analyzed ACE I/D polymorphism in 346 MDD patients and 210 healthy subjects using polymerase chain reaction technique.

Results

Comparing the two groups, no significant difference was observed with regard to either genotype distributions or allele frequencies of the I/D polymorphism of ACE gene.

Discussion

Our findings suggest that the ACE I/D polymorphism is not associated with MDD in Turkish case-control study. Further studies are still needed.

Major depressive disorder; angiotensin-converting enzyme; polymorphism

Introduction

Major depressive disorder (MDD) is a common psychiatric disease, often associated with morbidity and mortality. Although many factors were considered as the cause of this disease, its etiology has not been ascertained yet. Studies with families, twins and fosterlings reveal that genetic factors play an important role in its etiology11. Lohoff FW. Overview of the genetics of major depressive disorder. Curr Psychiatry Rep. 2010;12(6):539-46.. The prevalence of disease varies according to countries and age groups22. Prina AM, Cosco TD, Dening T, Beekman A, Brayne C, Huisman M. The association between depressive symptoms in the community, non-psychiatric hospital admission and hospital outcomes: a systematic review. J Psychosom Res. 2015;78(1):25-33.. Studies suggest that 10% to 15% of the general population will be exposed to clinical depression during their life11. Lohoff FW. Overview of the genetics of major depressive disorder. Curr Psychiatry Rep. 2010;12(6):539-46.. Although the etiopathogenesis of the disease is not fully understood yet, it has been estimated that a genetic susceptibility could be effective in the onset of MDD33. Lopizzo N, Bocchio Chiavetto L, Cattane N, Plazzotta G, Tarazi FI, Pariante CM, et al. Gene-environment interaction in major depression: focus on experience-dependent biological systems. Front Psychiatry. 2015;6:68.. Also, MDD is because of a complex genetic heterogeneity. Recent studies have shown that different genetic variants may contribute to the development of the MDD such as ACE gene polymorphism44. Hou Z, Yuan Y, Zhang Z, Hou G, You J, Bai F. The D-allele of ACE insertion/deletion polymorphism is associated with regional white matter volume changes and cognitive impairment in remitted geriatric depression. Neurosci Lett. 2010;479(3):262-6.

5. Wu Y, Wang X, Shen X, Tan Z, Yuan Y. The I/D polymorphism of angiotensin-converting enzyme gene in major depressive disorder and therapeutic outcome: a case-control study and meta-analysis. J Affect Disord. 2012;136(3):971-8.

6. Zill P, Baghai TC, Schüle C, Born C, Früstück C, Büttner A, et al. DNA methylation analysis of the angiotensin converting enzyme (ACE) gene in major depression. PLoS One. 2012;7(7):1-11.
-77. Hui L, Wu JQ, Ye MJ, Zheng K, He JC, Zhang X, et al. Association of angiotensin-converting enzyme gene polymorphism with schizophrenia and depressive symptom severity in a Chinese population. Hum Psychopharmacol. 2015;30(2):100-7..

ACE gene, localized on chromosome 17q23, undergoes a polymorphism deriving from the presence (insertion, I) or absence (deletion, D) within intron 16, of a 287 base pair ALU repeat sequence88. Inanır A, Yigit S, Tural S, Ozturk SD, Akkanet S, Habiboğlu A. Significant association between insertion/deletion polymorphism of the angiotensin-convertig enzyme gene and ankylosing spondylitis. Mol Vis. 2012;18:2107-13.. Although each allele are codominant effect to ACE levels, the homozygosity for I and D alleles have the lowest and highest levels of the enzyme, respectively. Additionally, the heterozygosity have no effect to serum ACE levels55. Wu Y, Wang X, Shen X, Tan Z, Yuan Y. The I/D polymorphism of angiotensin-converting enzyme gene in major depressive disorder and therapeutic outcome: a case-control study and meta-analysis. J Affect Disord. 2012;136(3):971-8.,99. Zintzaras E, Raman G, Kitsios G, Lau J. Angiotensin-converting enzyme insertion/deletion gene polymorphic variant as a marker of coronary artery disease: a meta-analysis. Arch Intern Med. 2008;168(10):1077-89.. ACE is also member of the renin-angiotensin system and acts a part in the conversion of angiotensin I to angiotensin II55. Wu Y, Wang X, Shen X, Tan Z, Yuan Y. The I/D polymorphism of angiotensin-converting enzyme gene in major depressive disorder and therapeutic outcome: a case-control study and meta-analysis. J Affect Disord. 2012;136(3):971-8.. Angiotensin II is a peptide hormone which acts as a stimulator of proinflammatory cytokines and interferes with hypothalamic-pituitary-adrenal (HPA) axis activation in response to stress55. Wu Y, Wang X, Shen X, Tan Z, Yuan Y. The I/D polymorphism of angiotensin-converting enzyme gene in major depressive disorder and therapeutic outcome: a case-control study and meta-analysis. J Affect Disord. 2012;136(3):971-8.,1010. Ising M, Holsboer F. Genetics of stress response and stress-related disorders. Dialogues Clin Neurosci. 2006;8(4):433-44.. It is mentioned from the effect of the brain renin-angiotensin system in regulation of mood1111. Inanir A, Yigit S, Tekcan A, Pinarli FA, Inanir S, Karakus N. Angiotensin converting enzyme and methylenetetrahydrofolate reductase gene variations in fibromyalgia syndrome. Gene. 2015;564(2):188-92.. It has been stated that ACE I/D polymorphism may be associated with suicide and MDD55. Wu Y, Wang X, Shen X, Tan Z, Yuan Y. The I/D polymorphism of angiotensin-converting enzyme gene in major depressive disorder and therapeutic outcome: a case-control study and meta-analysis. J Affect Disord. 2012;136(3):971-8.. ACE is responsible for degeneration of neurokinins that play an important role in regulation of emotions. Angiotensin II is both a potent neuropeptide and have essential roles in cognitive processes1212. Firouzabadi N, Shafiei M, Bahramali E, Ebrahimi SA, Bakhshandeh H, Tajik N. Association of angiotensin-converting enzyme (ACE) gene polymorphism with elevated serum ACE activity and major depression in an Iranian population. Psychiatry Res. 2012;200(2-3):336-42.. In some studies, it has been shown that ACE may contribute to the pathophysiology of psychiatric diseases by interacting with central dopamine77. Hui L, Wu JQ, Ye MJ, Zheng K, He JC, Zhang X, et al. Association of angiotensin-converting enzyme gene polymorphism with schizophrenia and depressive symptom severity in a Chinese population. Hum Psychopharmacol. 2015;30(2):100-7.. Therefore, it is important the investigation of ACE gene polymorphisms which are affecting an active to mood and personal stress. This case control study was designed to determine whether the ACE I/D gene polymorphism is related with susceptibility to MDD in Turkish population or not.

Material and methods

Subjects

In our study, 346 patients diagnosed with MDD (74 male and 272 female) and 210 healthy volunteers (75 male and 134 females as control group) who were recruited to Tokat Gaziosmanpasa University, Department of Psychiatry were included to the study. According to Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria, the patient group comprises individuals diagnosed with major depression. Both the study group and control group were recruited from the Turkish population. Subjects included to the study were greater than 18 years old. Informed written consent was obtained from all patients and subjects before enrollment to the study, according to the ethical guidelines of the 2008 Declaration of Helsinki and the investigation was approved by the ethical, investigation and biosecurity committee of Gaziosmanpasa University Faculty of Medicine.

Genotype determination

This study was conducted in Gaziosmanpasa University, Department of Medical Biology and Genetics laboratories. Blood samples were collected from patients and controls. Genomic DNA was isolated from whole venous blood samples using a commercial DNA isolation kit (Sigma-Aldrich, Germany). In addition, after isolated, the DNA should be stored at -20C. ACE gene I/D polymorphism genotypes were determined by polymerase chain reaction (PCR) using the primers and conditions described earlier88. Inanır A, Yigit S, Tural S, Ozturk SD, Akkanet S, Habiboğlu A. Significant association between insertion/deletion polymorphism of the angiotensin-convertig enzyme gene and ankylosing spondylitis. Mol Vis. 2012;18:2107-13.,1111. Inanir A, Yigit S, Tekcan A, Pinarli FA, Inanir S, Karakus N. Angiotensin converting enzyme and methylenetetrahydrofolate reductase gene variations in fibromyalgia syndrome. Gene. 2015;564(2):188-92.. Reactions were performed with 10 pmol of each primer: sense oligo, 5’-CTG GAG ACC ACT CCC ATC CTT TCT-3’, and antisense oligo, 5’-GAT GTG GCC ATC ACA TTC GTC AAG T-3’. Amplification was performed in a thermal cycler for 30 cycles with denaturation at 94ºC for 40 s, annealing at 56ºC for 40 s and extension at 72ºC for 40 s, followed by a final extension at 72ºC for 10 min. PCR products were analyzed on 2% agarose gels after staining with ethidium bromide and were visualized using a UV transilluminator. The polymorphisms detected by PCR were evident as an approximately 490-bp fragment in the presence of the insertion (I) allele and as an approximately 190-bp fragment in the absence of insertion (D) allele. In heterozygous samples, two bands (490 and 190 bp) were detected. In order to confirm the accuracy and reproducibility of this method, each PCR reaction included internal controls for each genotype. Second PCR was performed to confirm samples whose results were not clear.

Statistical analysis

All statistical analyses of data were performed using the computer software SPSS version 15.0 for Windows and OpenEpi Info software package program. Genotype distribution of the ACE gene and allele frequency between MDD patients and controls were compared by Chi-Square test. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated. Hardy-Weinberg equation was applied to the genotypes of the patients and controls. P values 0.05 or less were considered statistically significant.

Results

Demographic variables and baseline characteristics of patients were presented in Table 1. The mean age ± standard deviation (SD) was 38.12 ± 12.74 years in patients and 36.47 ± 9.33 years in control group. There were 74 (21.4%) males, 272 (78.6%) females and 75 (35.7%) males, 134 (63.8%) females in patient and control groups, respectively. The observed and expected frequencies of the polymorphism in both patient and control group were in Hardy-Weinberg equilibrium. It is determined that there was no statistical significant difference in the allele and genotype frequencies of ACE I/D polymorphism in patients and control groups (p > 0.05, OR 1.18, 95 % CI 0.91-1.51) (Table 2). Agarose gel electrophoresis patterns of ACE gene I/D polymorphisms were represented in Figure 1.

Table 1
Clinical and demographic characteristics of the patients with MDD and healthy controls

Table 2
Genotype and allele frequencies of ACE gene polymorphisms in MDD patient and control groups

Figure 1
Agarose gel electrophoresis patterns for I/D genotypes and genetic variations of ACE gene.

Discussion

In this study we assessed the association of ACE I/D polymorphism in patients with MDD. When we consider prevalence and etiologies of MDD, we think that the genetic background of MDD should be investigated. In this study, it was not found any association between patient and control groups in Turkish MDD population in terms of ACE I/D polymorphism. ACE, membrane-bound endopeptidase, is expressed in many tissues including brain1313. Wu Y, Wang X, Shen X, Tan Z, Yuan Y. The I/D polymorphism of angiotensin-converting enzyme gene in major depressive disorder and therapeutic outcome: a case-control study and meta-analysis. J Affect Disord. 2012;136(3):971-8.. It is reported that ACE in neuroepithelial cells degrades neurotransmitters such as substance P, which has a role in depression1414. Hong CJ, Wang YC, Tsai SJ. Association study of angiotensin I-converting enzyme polymorphism and symptomatology and antidepressant response in major depressive disorders. J Neural Transm. 2002;109(9):1209-14. and that angiotensin II interacts with dopamine in some specific parts of brain1515. Angunsri R, Sritharathikhun T, Suttirat S, Tencomnao T. Association of angiotensin-converting enzyme gene promoter single nucleotide polymorphisms and haplotype with major depression in a northeastern Thai population. J Renin Angiotensin Aldosterone Syst. 2009;10(3):179-84.. Angiotensin II, acting as a stimulator of proinflammatory cytokines, makes changes on the hypothalamic-pituitary-adrenal (HPA) axis activation that develops in response to stress. ACE gene variations play a significant role in the HPA axis hyperactivity in depression. It has shown that variations in the ACE gene have an important impact on the HPA axis hyperactivity found in depression1616. Baghai TC, Schule C, Zwanzger P, Minov C, Zill P, Ella R, et al. Hypothalamic-pituitary-adrenocortical axis dysregulation in patients with major depression is influenced by the insertion/deletion polymorphism in the angiotensin I-converting enzyme gene. Neurosci Lett. 2002;328(3):299-303.. Captopril, an ACE inhibitor, is proved to have an antidepressant effect1717. Vuckovic A, Cohen BM, Zubenko GS. The use of captopril in treatment-resistant depression: an open trial. Clin Psychopharmacol. 1991;11(6):395-6.. The fact that ACE gene variations affect serum enzyme level causes functional changes. ACE I/D polymorphism has been the subject of association studies related to various physiopathological conditions including mood disorder. It was reported that the depressive symptoms in schizophrenics was clearly associated with ACE I allele in the Chinese population77. Hui L, Wu JQ, Ye MJ, Zheng K, He JC, Zhang X, et al. Association of angiotensin-converting enzyme gene polymorphism with schizophrenia and depressive symptom severity in a Chinese population. Hum Psychopharmacol. 2015;30(2):100-7. and that D allele had a protective effect for schizophrenia in the Spanish population1818. Crescenti A, Gassó P, Mas S, Abellana R, Deulofeu R, Parellada E, et al. Insertion/deletion polymorphism of the angiotensin-converting enzyme gene is associated with schizophrenia in a Spanish population. Psychiatry Res. 2009;165(1-2):175-80.. The researchers were also interested in whether ACE gene polymorphism affected the responses to therapeutic agents. It was reported that high activity of ACE genotype was associated with unfavorable response to conventional therapy in schizophrenic patients1919. Illi A, Kampman O, Anttila S, Roivas M, Mattila KM, Lehtimäki T, et al. Interaction between angiotensin-converting enzyme and catechol-O-methyltransferase genotypes in schizophrenics with poor response to conventional neuroleptics. Eur Neuropsychopharmacol. 2003;13(3):147-51.. Kucukali et al. indicated that there was an association between D/D genotype and bipolar disorder in patients order and their first-degree relatives2020. Kucukali CI, Aydin M, Ozkok E, Bilge E, Zengin A, Cakir U, et al. Angiotensin-converting enzyme polymorphism in schizophrenia, bipolar disorders, and their first-degree relatives. Psychiatr Genet. 2010;20(1):14-9.. On the other hand, data collected previously suggested that ACE I/D polymorphism could possibly be a biological marker of depression2121. Kara M, Kara B, Erol D, Yuce H, Atmaca M, Tekederli I. The insertion/deletion of angiotensin converting enzyme is associated with major depression. Fırat Medical Journal. 2012;17(3):153-5.

22. Baghai TC, Schule C, Zwanzger P, Zill P, Ella R, Eser D, et al. Influence of a functional polymorphism within the angiotensin I-converting enzyme gene on partial sleep deprivation in patients with major depression. Neurosci Lett. 2003;339(3):223-6.

23. Baghai TC, Binder EB, Schule C, Salyakina D, Eser D, Lucae S, et al. Polymorphisms in the angiotensin-converting enzyme gene are associated with unipolar depression, ACE activity and hypercortisolism. Mol Psychiatry. 2006;11(11):1003-15.
-2424. Ancelin ML, Carrière I, Scali J, Ritchie K, Chaudieu I, Ryan J. Angiotensin-converting enzyme gene variants are associated with both cortisol secretion and late-life depression. Transl Psychiatry. 2013;3:e322.. On the basis of these findings, the studies related to the genetic background of the MDD patients will make an important contribution to the clarification of the relationship between ACE gene and MDD.

A meta-analysis evaluating the data of several studies indicated that there was no association between schizophrenia and ACE I/D polymorphism2525. Song GG, Lee YH. The insertion/deletion polymorphism in the angiotensin-converting enzyme and susceptibility to schizophrenia or Parkinson’s disease: A meta-analysis. J Renin Angiotensin Aldosterone Syst. 2015;16(2):434-42., and the same result was supported in a study with the Croatian population2626. Nadalin S, Buretić-Tomljanović A, Rubeša G, Jonovska S, Tomljanović D, Ristić S. Angiotensin-converting enzyme gene insertion/deletion polymorphism is not associated with schizophrenia in a Croatian population. Psychiatr Genet. 2012;22(5):267-8., in consistent with our study results. While it was reported that bipolar disorder was not associated with I/D polymorphism2727. Meira-Lima IV, Pereira AC, Mota GF, Krieger JE, Vallada H. Angiotensinogen and angiotensin converting enzyme gene polymorphisms and the risk of bipolar affective disorder in humans. Neurosci Lett. 2000;293(2):103-6., another study suggested that it was associated with I/D genotype in the Asian race2828. Zou YF, Wang F, Feng XL, Li WF, Pan FM, Huang F. Meta-analysis of ACE gene I/D polymorphism and bipolar disorder susceptibility. Nord J Psychiatry. 2011;65(4):276-82.. ACE gene polymorphism was reported not to be related to panic disorder2929. Shimizu E, Hashimoto K, Kobayashi K, Mitsumori M, Ohgake S, Koizumi H, et al. Lack of association between angiotensin I-converting enzyme insertion/deletion gene functional polymorphism and panic disorder in humans. Neurosci Lett. 2004;363(1):81-3.,3030. Olsson M, Annerbrink K, Westberg L, Melke J, Baghaei F, Rosmond R, et al. Angiotensin-related genes in patients with panic disorder. Am J Med Genet B Neuropsychiatr Genet. 2004;127B(1):81-4., although the frequency of I allele is higher in men than women3131. Bayoglu B, Cengiz M, Karacetin G, Uysal O, Kocabasoğlu N, Bayar R, et al. Genetic polymorphism of angiotensin I-converting enzyme (ACE), but not angiotensin II type I receptor (ATr1), has a gender-specific role in panic disorder. Psychiatry Clin Neurosci. 2012;66(2):130-7.. Another study stated that there was an association between ACE gene polymorphism and MDD only in female patients3232. Baghai TC, Schule C, Zill P, Deiml T, Eser D, Zwanzger P, et al. The angiotensin I converting enzyme insertion/deletion polymorphism influences therapeutic outcome in major depressed women, but not in men. Neurosci Lett. 2004;363(1):38-42., as consistent to our results. Arinami et al. found that D/D genotype increased sensitivity to affective disorder3333. Arinami T, Li L, Mitsushio H, Itokawa M, Hamaguchi H, Toru M. An insertion/deletion polymorphism in the angiotensin converting enzyme gene is associated with both brain substance P contents and affective disorders. Biol Psychiatry. 1996;40(11):1122-7.. However, mood disorders that started in childhood were reported not to be associated with ACE polymorphism3434. Dempster EL, Kiss E, Kapornai K, Daróczi G, Mayer L, Baji I, et al.; International Consortium for Childhood-Onset Mood Disorders. No evidence of an association between two genes, EDN1 and ACE, and childhood-onset mood disorders. Am J Med Genet B Neuropsychiatr Genet. 2010;153B(1):341-6.. Studies conducted to examine the association between MDD and ACE did not show any link with ACE I/D polymorphism1414. Hong CJ, Wang YC, Tsai SJ. Association study of angiotensin I-converting enzyme polymorphism and symptomatology and antidepressant response in major depressive disorders. J Neural Transm. 2002;109(9):1209-14.,3535. Segman RH, Shapira Y, Modai I, Hamdan A, Zislin J, Heresco-Levy U, et al. Angiotensin converting enzyme gene insertion/deletion polymorphism: case-control association studies in schizophrenia, major affective disorder, and tardive dyskinesia and a family-based association study in schizophrenia. Am J Med Genet. 2002;114(3):310-4.

36. Pauls J, Bandelow B, Rüther E, Kornhuber J. Polymorphism of the gene of angiotensin converting enzyme: lack of association with mood disorder. J Neural Transm. 2000;107(11):1361-6.

37. Furlong RA, Keramatipour M, Ho LW, Rubinsztein JS, Michael A, Walsh C, et al. No association of an insertion/deletion polymorphism in the angiotensin I converting enzyme gene with bipolar or unipolar affective disorders. Am J Med Genet. 2000;96(6):733-5.

38. Saab YB, Gard PR, Yeoman MS, Mfarrej B, El-Moalem H, Ingram MJ. Renin-angiotensin-system gene polymorphisms and depression. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(5):1113-8.
-3939. López-León S, Janssens AC, Hofman A, Claes S, Breteler MM, Tiemeier H, et al. No association between the angiotensin-converting enzyme gene and major depression: a case-control study and meta-analysis. Psychiatr Genet. 2006;16(6):225-6.. The same result was supported in Chinese population where it was reported that ACE gene polymorphism did not affect response to the treatment1313. Wu Y, Wang X, Shen X, Tan Z, Yuan Y. The I/D polymorphism of angiotensin-converting enzyme gene in major depressive disorder and therapeutic outcome: a case-control study and meta-analysis. J Affect Disord. 2012;136(3):971-8.. Also, Zill et al. suggest that aberrations in ACE promoter DNA methylation may be an underlying cause of MD4040. Zill P, Baghai TC, Schüle C, Born C, Früstück C, Büttner A, et al. DNA methylation analysis of the angiotensin converting enzyme (ACE) gene in major depression. PLoS One. 2012;7(7):e40479.. Depression were also significantly associated with an increase in cortisol secretion and, it is stated that ACE gene rs4295, rs4311, rs4343, rs4291, rs4333 and rs4351 variations influence cortisol secretion4141. Ancelin ML, Carrière I, Scali J, Ritchie K, Chaudieu I, Ryan J. Angiotensin-converting enzyme gene variants are associated with both cortisol secretion and late-life depression. Transl Psychiatry. 2013;3:322.. ACE gene A2350G polymorphism was closely associated with MDD among Iranian population1212. Firouzabadi N, Shafiei M, Bahramali E, Ebrahimi SA, Bakhshandeh H, Tajik N. Association of angiotensin-converting enzyme (ACE) gene polymorphism with elevated serum ACE activity and major depression in an Iranian population. Psychiatry Res. 2012;200(2-3):336-42.. Stewart et al. reported that there was no difference between MDD and control groups with regard to allele and genotype4242. Stewart JA, Kampman O, Huuhka M, Anttila S, Huuhka K, Lehtimäki T, Leinonen E. ACE polymorphism and response to electroconvulsive therapy in major depression. Neurosci Lett. 2009 ; 458(3): 122-5.. Considering this informations, we think that ACE I/D polymorphism was not related to the development of MDD in Turkish patients. Because the number of studies performed on the association of the ACE gene with Turkish MDD is limited, we think that the present study provides an important contribution to the literature.

Conclusions

In the present study, we not found a significant association between the ACE gene I/D polymorphism and MDD in Turkish population. The results cannot explain the role of ACE I/D polymorphism in the development of MDD. This polymorphism is not a susceptibility factor to MDD in the Turkish population. Although the present study does not provide any difference between the groups, we believe that there is a need for more comprehensive studies in different populations.

References

  • 1
    Lohoff FW. Overview of the genetics of major depressive disorder. Curr Psychiatry Rep. 2010;12(6):539-46.
  • 2
    Prina AM, Cosco TD, Dening T, Beekman A, Brayne C, Huisman M. The association between depressive symptoms in the community, non-psychiatric hospital admission and hospital outcomes: a systematic review. J Psychosom Res. 2015;78(1):25-33.
  • 3
    Lopizzo N, Bocchio Chiavetto L, Cattane N, Plazzotta G, Tarazi FI, Pariante CM, et al. Gene-environment interaction in major depression: focus on experience-dependent biological systems. Front Psychiatry. 2015;6:68.
  • 4
    Hou Z, Yuan Y, Zhang Z, Hou G, You J, Bai F. The D-allele of ACE insertion/deletion polymorphism is associated with regional white matter volume changes and cognitive impairment in remitted geriatric depression. Neurosci Lett. 2010;479(3):262-6.
  • 5
    Wu Y, Wang X, Shen X, Tan Z, Yuan Y. The I/D polymorphism of angiotensin-converting enzyme gene in major depressive disorder and therapeutic outcome: a case-control study and meta-analysis. J Affect Disord. 2012;136(3):971-8.
  • 6
    Zill P, Baghai TC, Schüle C, Born C, Früstück C, Büttner A, et al. DNA methylation analysis of the angiotensin converting enzyme (ACE) gene in major depression. PLoS One. 2012;7(7):1-11.
  • 7
    Hui L, Wu JQ, Ye MJ, Zheng K, He JC, Zhang X, et al. Association of angiotensin-converting enzyme gene polymorphism with schizophrenia and depressive symptom severity in a Chinese population. Hum Psychopharmacol. 2015;30(2):100-7.
  • 8
    Inanır A, Yigit S, Tural S, Ozturk SD, Akkanet S, Habiboğlu A. Significant association between insertion/deletion polymorphism of the angiotensin-convertig enzyme gene and ankylosing spondylitis. Mol Vis. 2012;18:2107-13.
  • 9
    Zintzaras E, Raman G, Kitsios G, Lau J. Angiotensin-converting enzyme insertion/deletion gene polymorphic variant as a marker of coronary artery disease: a meta-analysis. Arch Intern Med. 2008;168(10):1077-89.
  • 10
    Ising M, Holsboer F. Genetics of stress response and stress-related disorders. Dialogues Clin Neurosci. 2006;8(4):433-44.
  • 11
    Inanir A, Yigit S, Tekcan A, Pinarli FA, Inanir S, Karakus N. Angiotensin converting enzyme and methylenetetrahydrofolate reductase gene variations in fibromyalgia syndrome. Gene. 2015;564(2):188-92.
  • 12
    Firouzabadi N, Shafiei M, Bahramali E, Ebrahimi SA, Bakhshandeh H, Tajik N. Association of angiotensin-converting enzyme (ACE) gene polymorphism with elevated serum ACE activity and major depression in an Iranian population. Psychiatry Res. 2012;200(2-3):336-42.
  • 13
    Wu Y, Wang X, Shen X, Tan Z, Yuan Y. The I/D polymorphism of angiotensin-converting enzyme gene in major depressive disorder and therapeutic outcome: a case-control study and meta-analysis. J Affect Disord. 2012;136(3):971-8.
  • 14
    Hong CJ, Wang YC, Tsai SJ. Association study of angiotensin I-converting enzyme polymorphism and symptomatology and antidepressant response in major depressive disorders. J Neural Transm. 2002;109(9):1209-14.
  • 15
    Angunsri R, Sritharathikhun T, Suttirat S, Tencomnao T. Association of angiotensin-converting enzyme gene promoter single nucleotide polymorphisms and haplotype with major depression in a northeastern Thai population. J Renin Angiotensin Aldosterone Syst. 2009;10(3):179-84.
  • 16
    Baghai TC, Schule C, Zwanzger P, Minov C, Zill P, Ella R, et al. Hypothalamic-pituitary-adrenocortical axis dysregulation in patients with major depression is influenced by the insertion/deletion polymorphism in the angiotensin I-converting enzyme gene. Neurosci Lett. 2002;328(3):299-303.
  • 17
    Vuckovic A, Cohen BM, Zubenko GS. The use of captopril in treatment-resistant depression: an open trial. Clin Psychopharmacol. 1991;11(6):395-6.
  • 18
    Crescenti A, Gassó P, Mas S, Abellana R, Deulofeu R, Parellada E, et al. Insertion/deletion polymorphism of the angiotensin-converting enzyme gene is associated with schizophrenia in a Spanish population. Psychiatry Res. 2009;165(1-2):175-80.
  • 19
    Illi A, Kampman O, Anttila S, Roivas M, Mattila KM, Lehtimäki T, et al. Interaction between angiotensin-converting enzyme and catechol-O-methyltransferase genotypes in schizophrenics with poor response to conventional neuroleptics. Eur Neuropsychopharmacol. 2003;13(3):147-51.
  • 20
    Kucukali CI, Aydin M, Ozkok E, Bilge E, Zengin A, Cakir U, et al. Angiotensin-converting enzyme polymorphism in schizophrenia, bipolar disorders, and their first-degree relatives. Psychiatr Genet. 2010;20(1):14-9.
  • 21
    Kara M, Kara B, Erol D, Yuce H, Atmaca M, Tekederli I. The insertion/deletion of angiotensin converting enzyme is associated with major depression. Fırat Medical Journal. 2012;17(3):153-5.
  • 22
    Baghai TC, Schule C, Zwanzger P, Zill P, Ella R, Eser D, et al. Influence of a functional polymorphism within the angiotensin I-converting enzyme gene on partial sleep deprivation in patients with major depression. Neurosci Lett. 2003;339(3):223-6.
  • 23
    Baghai TC, Binder EB, Schule C, Salyakina D, Eser D, Lucae S, et al. Polymorphisms in the angiotensin-converting enzyme gene are associated with unipolar depression, ACE activity and hypercortisolism. Mol Psychiatry. 2006;11(11):1003-15.
  • 24
    Ancelin ML, Carrière I, Scali J, Ritchie K, Chaudieu I, Ryan J. Angiotensin-converting enzyme gene variants are associated with both cortisol secretion and late-life depression. Transl Psychiatry. 2013;3:e322.
  • 25
    Song GG, Lee YH. The insertion/deletion polymorphism in the angiotensin-converting enzyme and susceptibility to schizophrenia or Parkinson’s disease: A meta-analysis. J Renin Angiotensin Aldosterone Syst. 2015;16(2):434-42.
  • 26
    Nadalin S, Buretić-Tomljanović A, Rubeša G, Jonovska S, Tomljanović D, Ristić S. Angiotensin-converting enzyme gene insertion/deletion polymorphism is not associated with schizophrenia in a Croatian population. Psychiatr Genet. 2012;22(5):267-8.
  • 27
    Meira-Lima IV, Pereira AC, Mota GF, Krieger JE, Vallada H. Angiotensinogen and angiotensin converting enzyme gene polymorphisms and the risk of bipolar affective disorder in humans. Neurosci Lett. 2000;293(2):103-6.
  • 28
    Zou YF, Wang F, Feng XL, Li WF, Pan FM, Huang F. Meta-analysis of ACE gene I/D polymorphism and bipolar disorder susceptibility. Nord J Psychiatry. 2011;65(4):276-82.
  • 29
    Shimizu E, Hashimoto K, Kobayashi K, Mitsumori M, Ohgake S, Koizumi H, et al. Lack of association between angiotensin I-converting enzyme insertion/deletion gene functional polymorphism and panic disorder in humans. Neurosci Lett. 2004;363(1):81-3.
  • 30
    Olsson M, Annerbrink K, Westberg L, Melke J, Baghaei F, Rosmond R, et al. Angiotensin-related genes in patients with panic disorder. Am J Med Genet B Neuropsychiatr Genet. 2004;127B(1):81-4.
  • 31
    Bayoglu B, Cengiz M, Karacetin G, Uysal O, Kocabasoğlu N, Bayar R, et al. Genetic polymorphism of angiotensin I-converting enzyme (ACE), but not angiotensin II type I receptor (ATr1), has a gender-specific role in panic disorder. Psychiatry Clin Neurosci. 2012;66(2):130-7.
  • 32
    Baghai TC, Schule C, Zill P, Deiml T, Eser D, Zwanzger P, et al. The angiotensin I converting enzyme insertion/deletion polymorphism influences therapeutic outcome in major depressed women, but not in men. Neurosci Lett. 2004;363(1):38-42.
  • 33
    Arinami T, Li L, Mitsushio H, Itokawa M, Hamaguchi H, Toru M. An insertion/deletion polymorphism in the angiotensin converting enzyme gene is associated with both brain substance P contents and affective disorders. Biol Psychiatry. 1996;40(11):1122-7.
  • 34
    Dempster EL, Kiss E, Kapornai K, Daróczi G, Mayer L, Baji I, et al.; International Consortium for Childhood-Onset Mood Disorders. No evidence of an association between two genes, EDN1 and ACE, and childhood-onset mood disorders. Am J Med Genet B Neuropsychiatr Genet. 2010;153B(1):341-6.
  • 35
    Segman RH, Shapira Y, Modai I, Hamdan A, Zislin J, Heresco-Levy U, et al. Angiotensin converting enzyme gene insertion/deletion polymorphism: case-control association studies in schizophrenia, major affective disorder, and tardive dyskinesia and a family-based association study in schizophrenia. Am J Med Genet. 2002;114(3):310-4.
  • 36
    Pauls J, Bandelow B, Rüther E, Kornhuber J. Polymorphism of the gene of angiotensin converting enzyme: lack of association with mood disorder. J Neural Transm. 2000;107(11):1361-6.
  • 37
    Furlong RA, Keramatipour M, Ho LW, Rubinsztein JS, Michael A, Walsh C, et al. No association of an insertion/deletion polymorphism in the angiotensin I converting enzyme gene with bipolar or unipolar affective disorders. Am J Med Genet. 2000;96(6):733-5.
  • 38
    Saab YB, Gard PR, Yeoman MS, Mfarrej B, El-Moalem H, Ingram MJ. Renin-angiotensin-system gene polymorphisms and depression. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(5):1113-8.
  • 39
    López-León S, Janssens AC, Hofman A, Claes S, Breteler MM, Tiemeier H, et al. No association between the angiotensin-converting enzyme gene and major depression: a case-control study and meta-analysis. Psychiatr Genet. 2006;16(6):225-6.
  • 40
    Zill P, Baghai TC, Schüle C, Born C, Früstück C, Büttner A, et al. DNA methylation analysis of the angiotensin converting enzyme (ACE) gene in major depression. PLoS One. 2012;7(7):e40479.
  • 41
    Ancelin ML, Carrière I, Scali J, Ritchie K, Chaudieu I, Ryan J. Angiotensin-converting enzyme gene variants are associated with both cortisol secretion and late-life depression. Transl Psychiatry. 2013;3:322.
  • 42
    Stewart JA, Kampman O, Huuhka M, Anttila S, Huuhka K, Lehtimäki T, Leinonen E. ACE polymorphism and response to electroconvulsive therapy in major depression. Neurosci Lett. 2009 ; 458(3): 122-5.

Publication Dates

  • Publication in this collection
    Mar-Apr 2016

History

  • Received
    9 Nov 2015
  • Accepted
    7 Apr 2016
Faculdade de Medicina da Universidade de São Paulo Rua Ovídio Pires de Campos, 785 , 05403-010 São Paulo SP Brasil, Tel./Fax: +55 11 2661-8011 - São Paulo - SP - Brazil
E-mail: archives@usp.br