| Ference et al. 2012 (88 Ference BA, Yoo W, Alesh I, Mahajan N, Mirowska KK, Mewada A, et al. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis. J Am Coll Cardiol. 2012; 60(25):2631-9.)
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Combination studies with Mendelian randomization in meta-analysis (association of 9 SNPs in six different genes) to obtain the most accurate estimate of long-term effect of exposure to low concentrations of LDL-c, and its relationship with risk of CAD and the comparison with effect of lowered LDL-c by use of statins |
CAD risk reduction between 6-28% was observed in 9 SNPs evaluated. The variation of significance for LDL-c values were from - 16.68 to - 2.63 mg/dL. A log-linear variation between exposure to reduced LDL-c and the risk of CAD was verified. Among the 312,321 participants with different SNPs, a risk reduction of 54.5% (OR: 0.45) was found for each mmol/L or 38.7 mg/dL reduction in LDL-c. For 83,873 participants - score LDL-c in 6 SNPs, risk reduction was 53.2% for CAD. On the other hand, in 26 trials that included 169,138 participants treated with statins, risk reduction for CAD was 24% (OR: 0.44) for each 3 mmol/L or 116 mg/dL reduction in LDL-c |
9 polymorphisms were consistently associated with reduced risk of CAD as measured per unit of LDL-c reduction Protective effect is independent of the mechanism of LDL-c reduction What matters is not the reduction method, but the magnitude and duration of exposure to low concentrations of LDL-c A weighted LDL-c genetic score including 13 polymorphisms was associated with 2.13-fold increased risk of MI for each SD (34.1 mg/dL) increase in LDL-c |
| Voight et al. 2012 (55 Voight BF, Peloso GM, Orho-Melander M, Frikke-Schmidt R, Barbalic M, Jensen MK, et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet. 2012;380(9841):572-80.)
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Assessment of cardiovascular outcomes such as myocardial infarction in populations with genetically high HDL, through Mendelian randomization of SNPs |
Meta-analysis data of 7 cohorts with 19,840 patients of 15 locirelated to high HDL-c plasma levels, 6 associated with reduction of MI but presenting pleiotropic effects of reduction in triglycerides and LDL-c. The remaining SNPs have no association with reduction in MI, and SNP rs16988929 on chromosome 20q13 showed increased risk of MI. In the 20 studies (13 case-control and six cohort studies) with a total of 116,320,000 participants, there was no association between LIPG Asn396Ser and IM risk reduction |
The genetic variant LIPG Asn 396Ser, which raises HDL, did not reduce MI The Score which combined 14 variants related to HDL were not associated with AMI only The data challenge the relation between the increase in HDL and lower risk of AMI The AIM-HIGH trial, which added niacin on statin therapy, showed no lower risk of cardiovascular events, either |
| Lamon et al. 2010 (99 Lamon-Fava S, Asztalos BF, Howard TD, Reboussin DM, Horvath KV, Schaefer EJ, et al. Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women. Clin Endocrinol (Oxf). 72(2):169-75.)
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Information about metabolic effects derived from the response of the gene involved with different subclasses of lipoproteins of hepatic lipase |
Carriers of the ESR1 PvuII or IVS1-1505 variants had lower plasma TG concentrations and higher plasma HDL-c, alfa1 and pre alfa-1 HDL, apo A-I and alfa-1 levels after hormone therapy than wild-type carriers. Carriers of the N291S and D9N variants in the lipoprotein lipase gene had higher levels of lipoproteins and lower levels of alfa-2 HDL |
Variations in gene lociare involved in the lipid metabolism, as well as subpopulations of TG-rich and HDL lipoproteins. SNPs in ESR1, CETP and LPL had significant effects on baseline plasma levels of these populations. Polymorphisms in genes involved in lipid metabolism do not explain much of the lipid variability and lipoproteic subfractions response to hormone therapy |
| Rosa et al. 2012 (1515 Aledo R, Alonso R, Mata P, Llorente-Cortés V, Padró T, Badimon L. LRP1 gene polymorphisms are associated with premature risk of cardiovascular disease in patients with familial hypercholesterolemia. Rev Esp Cardiol (Engl Ed). 2012;65(9):807-12.)
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Presence of early cardiovascular disease in patients with familial hypercholesterolemia and association with polymorphisms |
Significant association with polymorphism c.677c>T (rs 1799986) and early CAD, and effect on mutation of low density lipoprotein receptor in the dominant model (CT TT versusCC: OR=1.95; 95CI 1.08 - 3.48; p=0.029) |
Polymorphism c.677C>T is associated with increased chance of early cardiovascular disease in patients with familial hypercholesterolemia |
| Taegtmeyer et al. 2011 (11 Taegtmeyer AB, Breen JB, Smith J, Rogers P, Kullak-Ublick GA, Yacoub MH, et al. Effect of ABCB1 genotype on pre- and post-cardiac transplantation plasma lipid concentrations. J Cardiovasc Transl Res. 2011;4(3):304-12.)
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Association of genetic variation of ABCB1and plasma levels of LDL-c in patients with advanced heart failure |
Association between LDL-C in patients before transplant with the C345T genotype and G2677T/A-C3435T, C1236T-G2677T/A-C3435T haplotypes. Carriers of the T allele at all loci(n=77) had higher levels of LDL-C compared to non-carriers of the allele (n=24, p=0.025) |
The ABCB1 haplotype is associated with fasting LDL-c plasma levels in patients with advanced heart failure. However, this finding was not observed after 1 year of cardiac transplantation |
| Cerda et al. 2010 (2020 Cerda A, Genvigir FD, Arazi SS, Hirata MH, Dorea EL, Bernik MM, et al. Influence of SCARB1 polymorphisms on serum lipids of hypercholesterolemic individuals treated with atorvastatin. Clin Chim Acta. 2010;411(9-10):631-7.)
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Relation between 3 SNPs SCARB1 with hypercholesterolemia in a Brazilian population, and the influence of their variations on response to treatment with atorvastatin |
The c.726 54C>T allele was associated with higher levels of LDL-c in normolipidemic (NL) patients, with increased levels of APO B and APOB/APOAL in hypercholesterolemics (HC) (p<0.05). Carriers of the CETP TaqlB B2 allele had much higher levels of HDL-c (p<0.0001) |
The studied polymorphisms are associated with serum lipid levels in healthy pediatric patients. It highlights the potential of early prediction of an adverse lipid profile |
| Salazar et al. 2010 (1616 Salazar LA, Colivoro K, Diaz A, Sepúlveda S, Cuevas A, Saavedra N, et al. Association between single nucleotide polymorphism of adiponectin gene and coronary artery disease in Southern Chilean subjects. Rev Chil Cardiol. 2010;29(2):214-20.)
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CAD risk in a Chilean population, associated with 45 TMJ polymorphism (rs2241766) in the gene encoding adiponectin (ADIPOQ) |
The results showed that the presence of the G allele in the 45T>G polymorphism of ADIPOQ gene doubled the risk of CAD in the Chilean study population (OR=2.06; 95CI 1.36-3.14) |
First finding of relationship between 45T>G polymorphism of ADIPOQ gene and CAD in a Chilean population |
| Zintzaras et al. 2009 (2121 Zintzaras E, Kitsios GD, Triposkiadis F, Lau J, Raman G. APOE gene polymorphisms and response to statin therapy. Pharmacogenomics J. 2009;9(4):248-57.)
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Response of plasma lipid values to treatment with statins between genetic variants of the APOE gene (e2 carriers, homozygotes e3e3 and e4 carriers) |
The mean reduction of total cholesterol was significant for all variants - e2 carriers: Delta mu=-27.7% (-32.5 to -22.8%), e3e3: Delta mu=-25.3% (-28 to -22.6%) and e4 carriers: Delta mu=-25.1 (-29.3 to -21%) |
Non-significant results of APOE genotypic variation regarding lipid plasma levels. Its suggests that there is little reason to consider the use of APOE genetic testing for guiding treatment with statins |
| Smart et al. 2009 (2222 Smart MC, Dedoussis G, Louizou E, Yannakoulia M, Drenos F, Papoutsakis C, et al. APOE, CETP and LPL genes show strong association with lipid levels in Greek children. Nutr Metab Cardiovasc Dis 2010;20(1):26-33.)
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Children evaluation by the Gendai study on variants in the genes for lipoprotein lipase, CETP-Taq1B, APO E, APOA5, APOA4 and APOC3 regarding plasma levels of lipoproteins |
Carriers of the epsilon4 APOE variant, compared to epsilon3/epsilon3 homozygotes and epsilon carriers, have higher levels of total cholesterol (p=0.0001) and LDL-c (p=0.0001). Carriers of the TAqlB B2 CETP allele have higher levels of HDL-c (P=0.0001) and TC |
These common variants are associated with plasma levels of healthy pediatric patients |
| Lindi et al. 2008 (2323 Lindi V, Schwab U, Louheranta A, Vessby B, Hermansen K, Tapsell L, et al. The G-250A polymorphism in the hepatic lipase gene promoter is associated with changes in hepatic lipase activity and LDL cholesterol: The KANWU Study. Nutr Metab Cardiovasc Dis 2008;18(2):88-95.)
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The effects of G-250A polymorphism in the activity of the hepatic lipase, serum lipid profile, and insulin sensitivity |
The A-250A genotype was associated with high levels of LDL-c (p=0.03 for the 3 genotypes). In the group with monounsaturated fatty acids diet, patients with A-250A genotype showed strong decrease in LDL-c compared to other genotypes (p = 0.007). The -250A allele was associated with low activity of hepatic lipase (p<0.001). The diet did not affect the activity levels of hepatic lipase among the 3 groups |
The A-250A genotype of the hepatic lipase gene was associated with high plasma levels of LDL-c. Nonetheless, those patients who used diets rich in monounsaturated fatty acids showed reductions in serum levels of LDL-c especially in patients with genotype A-250A |
| Caamaño et al. 2008 (1717 Caamaño JM, Pacheco A, Lanas F, Salazar LA. Single nucleotide polymorphisms in ABCG5 and ABCG8 genes in Chilean subjects with polygenic hypercholesterolemia and controls. Clin Chem Lab Med. 2008;46(11):1581-5.)
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Association between ABCG5 and ABCG8 polymorphisms and the presence of hypercholesterolemia in Chilean individuals |
The frequency of homozygous genotypes for the ABCG5 1950>G polymorphism was higher for patients with hypercholesterolemia compared to controls (42 versus 10%, p<0.001). Hypercholesterolemic individuals carrying the GG genotype for 251A > G had higher levels of HDL-c compared to all other genotypes (p=0.02) |
The data show an association between ABCG5 1950 > G polymorphism and hypercholesterolemia. The small size of the sample was a limitation |
| Unno et al. 2006 (1414 Unno N, Sakaguchi T, Nakamura T, Yamamoto N, Sugatani J, Miwa M. et al. A single nucleotide polymorphism in the plasma PAF acetylhydrolase gene and risk of atherosclerosis in Japanese patients with peripheral artery occlusive disease. J Surg Res. 2006;134(1):36-43.)
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Presence of PAF acetylhydrolase (PAF-AH) in genetic polymorphism G994 - T, exon 9, in patients with peripheral arterial occlusive disease and the association between polymorphism and hypercholesterolemia in the risk of atherosclerosis |
Plasma activity of PAF-AH was associated with plasma levels of total cholesterol and LDL, and inversely related to plasma HDL in patients with normal genotype (GG) and peripheral arterial occlusive disease |
The association between plasma polymorphism of the PAF-AH gene and hypercholesterolemia may increase the risk |
| Fiengenbaum et al. 2005 (1111 Fiegenbaum M, Silveira FR, Van der Sand CR, Van der Sand LC, Ferreira ME, Pires RC, et al. Determinants of variable response to simvastatin treatment: the role of common variants of SCAP, SREBF-1a and SREBF-2 genes. Pharmacogenomics J. 2005;5(6):359-64.)
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The effect of SNPs in sterol regulatory element-binding proteins SREBF-1a, SREBF-2 and SREBF (SCAP) on lipid reducing response mediated by the use of simvastatin |
Carriers of the SCAP 2386G allele have greater decrease in plasma total cholesterol compared to 2386 allele homozygotes |
The results suggest that polymorphism in the gene SCAP 2386A>G was a significant predictor of response to treatment with statin for levels of total cholesterol and triglycerides |
| Fjuita et al. 2005 (1818 Fujita Y, Ezura Y, Bujo H, Nakajima T, Takahashi K, Kamimura K, et al. Association of nucleotide variations in the apolipoprotein B48 receptor gene (APOB48R) with hypercholesterolemia. J Hum Genet. 2005;50(4):203-9.)
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Predisposing factors for phenotypic characteristics of high total cholesterol (T-Cho) and their association with two variants of APOB48R |
Significant correlation between genotypic variations of A419P and total cholesterol levels was observed. Among the homozygous carriers of the G allele (n=265), heterozygous carriers of the G allele (n=78), and homozygous carriers of the C allele (n=9), total cholesterol levels indicated a co-dominant effect of the C allele of increase in total cholesterol (r=0.15, p=0.007). A similar effect was observed for c.934-960/Del (r=0.13, p=0.015) |
Variations in APOB48R and other genes located closely are among the many factors involved in hypercholesterolemia |
| Fan et al. 2005 (1010 Fan YM., Dastidar P, Jokela H, Punnonen R, Lehtimäki T. Hepatic lipase C-480T genotype-dependent benefit from long-term hormone replacement therapy for atherosclerosis progression in postmenopausal women. J Clin Endocrinol Metab. 90(6):3786-92.)
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Hormone replacement therapy and the progression of atherosclerosis over a follow-up period of 5 years |
A significant association between HRT and genotypes of hepatic lipase was found for increased atherosclerosis severity score (ASC) (p=0.046). In patients with T allele, ASC progression was significantly faster in the control group compared with the HRT (p=0.0006) group, while the CC genotype showed no significant differences |
The results suggest that the beneficial effect of HRT on the progression of atherosclerosis was restricted to women carriers of the T allele |
| Poliseckil et al. 2005 (1212 Poliseckil E, Peter I, Simon JS, Hegele RA, Robertson M, Ford I, et al. Genetic variation at the NPC1L1 gene locus, plasma lipoproteins and heart disease risk in the elerly. J Lipid Res. 2010;51(5):1201-7.)
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Effects on lipid levels and prevalence/incidence of CAD as well as response to pravastatin in reducing plasma lipid profile, and the five variants of the NPC1L1 gene |
Homozygotes for alleles of four NPC1L1s (-18 A>C, L272L, V1296V and U3_28650 A > G) had 2-8% higher levels of LDL-c than homozygotes carrying common alleles (p<0.05). Homozygotes for rare alleles also had a significant increase in risk of CV events (OR 1.5-167; p<0.02) |
Variations in the Niemann-Pick C1-lie 1 protein (NPC1L1) gene are associated with the levels of LDL-c and risk of cardiovascular disease |
| Chasman et al. 2004 (1313 Chasman DI, Posada D, Subrahmanyan L, Cook NR, Stanton VP Jr, Ridker PM. Pharmacogenetic study of statin therapy and cholesterol reduction. JAMA. 2004;291(23):2821-7.)
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Lipid metabolism and response to therapy with pravastatin and its relationship to genetic variations of 148 SNPs in 10 genes |
When compared to homozygotes for the major allele of one of the SNPs, those with a single copy of the minor allele had 22% less reduction in total cholesterol (p =0.01), with an absolute difference of 9.2 mg/dL (95CI 3.8 - 14.6 mg/dL), and 19% less reduction in LDL-c (p=0,005), with an absolute difference of 6.4 mg/dL (95CI 2.2-10.6 g/dL) |
Heterozygotes for the genetic variant of the HMG-CoA reductase gene may have smaller reductions in cholesterol when treated with pravastatin |
| Ono et al. 2003 (1919 Ono S, Ezura Y, Emi M, Fujita Y, Takada D, Sato K, et al. A promoter SNP (-1323T>C) in G-substrate gene (GSBS) correlates with hypercholesterolemia. J Hum Genet. 2003;48(9):447-50.)
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Association between SNP (-1323T>C) promoter/GSBS gene and plasma levels of total cholesterol |
Of the 341 carriers of the T allele, approximately 80% had hypercholesterolemia versus 44% of the 27 individuals who did not carry this allele (p=0.0001) |
Significant increases in total cholesterol were associated with the SNP promoter (-1323T>C) and with the GSBS gene, which may play a role in plasma lipoprotein levels |
| Stanislovaitiene et al. 2013 (2424 Stanislovaitiene D, Lesauskaite V, Zaliuniene D, Smalinskiene A, Gustiene O, Zaliaduonyte-Peksiene D, et al. SCARB1 single nucleotide polymorphism (rs5888) is associated with serum lipid profile and myocardial infarction in na age and gender-denpendent manner. Lipids in Health and Disease 2013;12:24.)
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Impact of SCARB1 rs5888 SNP on lipid profile and its association with CAD in a Lithuanian population |
Men with TT genotype had higher levels of TC and TGC than older men who had higher HDL-c levels. Younger women with TT genotype had lower levels of LDL compared to the CC genotype. The frequency of the SCARB1 TT genotype among older individuals in the MI group was lower than that of the control group |
SCARB1 polymorphism is associated with age and gender regarding risk of atheromatous disease and heart failure |
