Genome-Wide Association Study of Coronary Artery Disease

Ogawa, Naomi; Imai, Yasushi; Morita, Hiroyuki; Nagai, Ryozo

doi:10.4061/2010/790539

Cited by 16 publications

(14 citation statements)

References 61 publications

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“…Massive genome-wide-association studies (GWAS) and meta-analysis have been performed to identify common gene variants that influence susceptibility to CAD. So far, about 28 loci have been have been identified among Caucasians and African Americans [73,74,75,76,77,78,79,80]. Some of these loci are also associated with risks for other diseases and traits.…”

Section: Genome Wide Association Studiesmentioning

confidence: 99%

The effect of hepatic lipase on coronary artery disease in humans is influenced by the underlying lipoprotein phenotype

Brunzell

Zambón

Deeb

2012

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Increased or decreased hepatic lipase (HL) activity has been associated with coronary artery disease (CAD). This is consistent with the findings that gene variants that influence HL activity were associated with increased CAD risk in some population studies but not in others. In this review, we will explain the conditions that influence the effects of HL on CAD. Increased HL is associated with smaller and denser LDL (sdLDL) and HDL (HDL3) particles, while decreased HL is associated with larger and more buoyant LDL and HDL particles. The effect of HL activity on CAD risk is dependent on the underlying lipoprotein phenotype or disorder. Central obesity with hypertriglyceridemia (HTG) is associated with high HL activity that leads to the formation of sdLDL that is proatherogenic. In the absence of HTG, where large buoyant cholesteryl ester-enriched LDL is prominent, elevation of HL does not raise the risk for CAD. In HTG patients, drug therapy that decreases HL activity selectively decreases sdLDL particles, an antiatherogenic effect. Drug therapy that raises HDL2 cholesterol has not decreased the risk for CAD. In trials where inhibition of cholesterol ester transfer protein (CETP) or HL occurs, the increase in HDL2 most likely is due to inhibition of catabolism of HDL2 and impairment of reverse cholesterol transport (RCT). In patients with isolated hypercholesterolemia, but with normal triglyceride levels and big-buoyant LDL particles, an increase in HL activity is beneficial; possibly because it increases RCT. Drugs that lower HL activity might decrease the risk for CAD only in hypertriglyceridemic patients with sdLDL by selectively clearing sdLDL particles from plasma, which would override the potentially pro-atherogenic effect on RCT.

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Section: Genome Wide Association Studiesmentioning

confidence: 99%

The effect of hepatic lipase on coronary artery disease in humans is influenced by the underlying lipoprotein phenotype

Brunzell

Zambón

Deeb

2012

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…Until now, many single-nucleotide polymorphisms (SNPs) of candidate genes as well as of regulatory loci have been discovered (Ogawa et al, 2010;The IBC 50K CAD Consortium, 2011). In 2007, independent genome-wide association studies revealed nine highly correlated SNPs (r 2 > 0.8) in a new locus in the region of chromosome 9 (9p21.3), showing the greatest association with heterogeneous CAD of all of the loci analyzed so far (Helgadottir et al, 2007;McPherson et al, 2007;Samani et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

The rs10757278 Polymorphism of the 9p21.3 Locus Is Associated with Premature Coronary Artery Disease in Polish Patients

Niemiec

Górczyńska-Kosiorz²,

Iwanicki³

et al. 2012

Genetic Testing and Molecular Biomarkers

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Recently, genome-wide association studies have revealed a locus associated with coronary artery disease (CAD) and myocardial infarction, namely, 9p21.3. Its participation in the conditioning of the disease has been proven in many populations of European descent, but not yet in Slavs. Allelic variants of the rs10757278 polymorphism functionally affect the activity of the 9p21.3 locus; therefore, we conducted a study to determine whether the rs10757278 is associated with premature CAD in Polish patients. We studied 320 subjects aged 25-55 years, divided into two groups matched by sex and age: (1) patients with angiographically proven premature CAD (n = 160), and (2) blood donors as a control group (n = 160). The rs10757278 was genotyped using the method of fluorescently labeled allelespecific oligonucleotides. The frequency of the G allele was significantly higher in patients than in controls (58.2% vs. 42.8%, respectively, p = 0.011) and was similar to the frequency of the GG homozygotes (30.6% vs. 17.5%, respectively, p = 0.006). Both the GG homozygosity (odds ratio [OR] = 2.08, 95% confidence interval [CI]: 1.19-3.66) as well as the G allele (OR = 1.49, 95% CI: 1.08-2.07) have been associated with CAD in the analyzed population. These variants may be considered as risk factors, also in the Polish population.

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“…Several gene variants have been related to cardiovascular risk or risk factors [25], [26]. However, this may be the first time that genetic variation in the vitamin C transporter gene SLC23A2 is tested in relation to cardiovascular disease, hence the results require replication.…”

Section: Discussionmentioning

confidence: 97%

Variation in the Sodium-Dependent Vitamin C Transporter 2 Gene Is Associated with Risk of Acute Coronary Syndrome among Women

et al. 2013

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BackgroundVitamin C is associated with a lower risk of coronary heart disease possibly due to its anti-oxidative effects, beneficial effects on endothelial function and importance in collagen synthesis. The sodium-dependent vitamin C transporter 2 is responsible for the transport of vitamin C into various cells and malfunction of this protein leads to reduced vitamin C in tissue, including the arterial wall. We tested the hypothesis that candidate variations rs6139591 and rs1776964 in the gene coding for sodium-dependent vitamin C transporter 2 are associated with development of acute coronary syndrome.DesignIn the Danish Diet, Cancer and Health cohort study, we performed a case-cohort study among 57,053 subjects aged 50–64 years.ResultsDuring a mean follow-up period of 6.4 years, we identified 936 cases and randomly selected a sub-cohort (n = 1,580) with full information on genotypes and covariates. Using Cox proportional hazard models, we found that women with the rs6139591 TT genotype and a lower than median dietary vitamin C intake had a higher risk of acute coronary syndrome compared with those with the CC genotype (adjusted HR 5.39, 95% confidence interval, 2.01–14.50). We also observed a not as strong but positive although inconsistent association for women at a higher than median intake of vitamin C rich food. For the rs1776964 polymorphism, we found a higher risk (adjusted HR 3.45, 95% CI, 1.16–10.28) among TT-homozygous women with higher than median vitamin C intake compared with the CC genotype and low vitamin C intake. Among men, weaker and non-significant associations were observed for both polymorphisms.ConclusionGenetic variation in the sodium-dependent vitamin C transporter 2 is associated with risk of incident acute coronary syndrome in women. The genotype effects may not be fully compensated by a higher intake of vitamin C rich food.

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Genome-Wide Association Study of Coronary Artery Disease

Cited by 16 publications

References 61 publications

The effect of hepatic lipase on coronary artery disease in humans is influenced by the underlying lipoprotein phenotype

The effect of hepatic lipase on coronary artery disease in humans is influenced by the underlying lipoprotein phenotype

The rs10757278 Polymorphism of the 9p21.3 Locus Is Associated with Premature Coronary Artery Disease in Polish Patients

Variation in the Sodium-Dependent Vitamin C Transporter 2 Gene Is Associated with Risk of Acute Coronary Syndrome among Women

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