Association study between the 1287 A/G exonic polymorphism of the norepinephrine transporter (NET) gene and obsessive-compulsive disorder in a Brazilian sample

Estudo da associação entre o polimorfismo exônico 1287 A/G do gene transportador da norepinefrina e o transtorno obsessivo-compulsivo em uma amostra brasileira

LETTERS TO THE EDITORS

Association study between the 1287 A/G exonic polymorphism of the norepinephrine transporter (NET) gene and obsessive-compulsive disorder in a Brazilian sample

Estudo da associação entre o polimorfismo exônico 1287 A/G do gene transportador da norepinefrina e o transtorno obsessivo-compulsivo em uma amostra brasileira

Dear Editor,

Obsessive-compulsive disorder (OCD) is a chronic, severely debilitating anxiety disorder, characterized by intrusive and senseless thoughts and impulses (obsessions) and by repetitive behaviors or mental acts (compulsions), with a lifetime prevalence of 2 to 3%. Data from family, twin and segregation studies have shown that genetic factors contribute to the expression of the disorder.¹ An essential step to understanding the genetics of OCD is the localization and characterization of the genes that confer susceptibility to the disorder.

Since there are reports that some drugs used in the treatment of OCD, like clomipramine and venlafaxine, act on the noradrenergic system among other systems² and that young unmedicated OCD subjects excrete in the urine more adrenaline and homovanillic acid than healthy controls,³ it is hypothesized that the noradrenergic system may be related to the pathophysiology of OCD. Therefore, the norepinephrine transporter (NET) gene became a candidate target for genetic studies of this disorder. To our knowledge, there is no previous investigation of the NET gene as a susceptibility gene for OCD.

NET is a 617-amino acid protein and its gene (SLC6A2) is located on chromosome 16q.12.2, consisting of 14 exons (protein coding regions).⁴ The silent polymorphism 1287 A/G (rs5569), located in the exon 9, has been previously studied in other psychiatric disorders, such as schizophrenia, bipolar disorder, major depression, Tourette syndrome and panic disorder. These investigations produced inconclusive results so far.

The present study investigated the 1287 A/G variant (rs5569) in 75 DSM-IV OCD patients and 317 matched healthy controls. This study was previously approved by the Clinical Hospital Ethics Committee and all participants gave their written informed consent. Genomic DNA was extracted from venous blood samples and the exonic silent polymorphism (1287 A/G – rs5569) was analyzed as described by Jönsson et al.⁵ PCR products were resolved on 2% agarose gels and visualized by ultra-violate light after ethidium bromide staining. We used a chi-square test for the analysis of the differences of allele and genotype frequencies between OCD patients and controls.

The genotypic distributions were in Hardy-Weinberg equilibrium. We did not find differences in the allelic (OR = 1.14 0.74 < OR < 1.75; X² = 0.38; 1 d.f.; p = 0.53) and genotypic (X² = 0.51; 2 d.f.; p = 0.77) distributions (Table 1). Our results do not support the association between the 1287 A/G polymorphism in the NET gene with OCD in our Brazilian sample.

Acknowledgments

This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) to Vallada H and Miguel EC and from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) to Miguita K.

Karen Miguita, Quirino Cordeiro, Roseli Gedanke Shavitt, Euripedes Constantino Miguel, Homero Vallada

Department of Psychiatry, Clinical Hospital, Medical School, Universidade de São Paulo (USP), São Paulo (SP), Brazil

References

1. Hounie AG, Brotto AS, Diniz J, Chacon PJ, Miguel EC. Transtorno obsessivo-compulsivo: possíveis subtipos. Rev Bras Psiquiatr. 2001;23(Supl2):13-6.

2. Albert U, Aguglia E, Maina G, Bogetto F. Venlafaxine versus clomipramine in the treatment of obsessive-compulsive disorder: a preliminary single-blind, 12-week, controlled study. J Clin Psychiatry. 2002;63(11):1004-9.

3. Oades RD, Ropcke B, Eggers C. Monoamine activity reflected in urine of young patients with obsessive compulsive disorder, psychosis with and without reality distortion and healthy subjects: an explorative analysis. J Neural Transm Gen Sect. 1994;96(2):143-59.

4. Bruss M, Kunz J, Lingen B, Bonisch H. Chromosomal mapping of the human gene for the tricyclic antidepressant-sensitive noradrenaline transporter. Hum Genet. 1993;91(3):278-80.

5. Jonsson EG, Nothen MM, Gustavsson JP, Neidt H, Bunzel R, Propping P, Sedvall GC. Polymorphisms in the dopamine, serotonin, and norepinephrine transporter genes and their relationships to monoamine metabolite concentrations in CSF of healthy volunteers. Psychiatry Res. 1998;79(1):1-9.

Financing: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (grant # 99/08560-6); and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) (number # 8817)

Conflict of interests: None

Publication Dates

• Publication in this collection
  26 June 2006
• Date of issue
  June 2006