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The association between the DNAH11 rs10248618 SNP and serum lipid traits, the risk of coronary artery disease, and ischemic stroke.

ABSTRACT: Previous genome-wide association studies have shown that the rs10248618 single nucleotide polymorphism (SNP) in the dynein axonemal heavy chain 11 gene (DNAH11) has been associated with serum high-density lipoprotein cholesterol (HDL-C) levels. However, little is known about such association in the Chinese population. The present study was performed to clarify the association between the DNAH11 rs10248618 SNP and serum lipid traits and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Guangxi Han population. Genotypes of the DNAH11 rs10248618 SNP in 1,213 unrelated patients (CAD, 600 and IS, 613) and 631 healthy controls were determined by snapshot technology. The genotypic and allelic frequencies of the SNP were significantly different between the CAD/IS patients and the controls (P < 0.01 for all). The CT/TT genotypes and the T allele were associated with an increased risk of CAD and IS (CAD: P < 0.01 for CT/TT vs. CC and T vs. C; IS: P < 0.01 for CT/TT vs. CC and T vs. C). The CT/TT genotypes in the healthy controls, but not in CAD or IS patients, were associated with a decreased serum HDL-C and apolipoprotein (Apo) A1 concentration. These results suggest that the DNAH11 rs10248618 SNP is associated with the risk of CAD and IS in our study population. It is likely to increase the risk of CAD and IS by reducing serum HDL-C and ApoA1 levels.

SUBMITTER: Zhou YG

PROVIDER: S-EPMC6962952 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The association between the DNAH11 rs10248618 SNP and serum lipid traits, the risk of coronary artery disease, and ischemic stroke.

Zhou Yong-Gang YG Yin Rui-Xing RX Wu Jie J Zhang Qing-Hui QH Chen Wu-Xian WX Cao Xiao-Li XL

International journal of clinical and experimental pathology 20180901 9

Previous genome-wide association studies have shown that the rs10248618 single nucleotide polymorphism (SNP) in the dynein axonemal heavy chain 11 gene (DNAH11) has been associated with serum high-density lipoprotein cholesterol (HDL-C) levels. However, little is known about such association in the Chinese population. The present study was performed to clarify the association between the DNAH11 rs10248618 SNP and serum lipid traits and the risk of coronary artery disease (CAD) and ...[more]

PMID: 31949857

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Project description:Previous genome-wide association studies have showed that the rs12670798 variant in the dynein axonemal heavy chain 11 gene (DNAH11) is associated with some serum lipid phenotypes. The present study was undertaken to detect the DNAH11 rs12670798 variant and G × E interactions on serum lipid levels, coronary heart disease (CHD), ischemic stroke (IS), and the lipid-lowering efficacy of atorvastatin in the Chinese Han population. This study included 1,108 unrelated patients (CHD, 568 and IS, 540) and 541 healthy controls. Genotypes of the DNAH11 rs12670798 were determined by the Snapshot technology. A total of 724 hyperlipidemic patients were treated with atorvastatin calcium tablet 20 mg per day for 8 weeks after genotyping. Serum total cholesterol (TC) levels in controls were different among the three genotypes of the rs12670798 (P = 0.019), the C allele carriers had higher TC levels than the C allele non-carriers. The C allele carriers were associated with an increased risk of CHD (CT genotype: OR = 1.345, 95% CI = 0.975-1.855, P = 0.071; CC genotype: OR = 1.590, 95% CI = 1.109-2.278, P = 0.012). The C allele carriers were also associated with an increased risk of IS (CT genotype: OR = 1.597, 95% CI = 1.153-2.213, P = 0.005; CC genotype: OR = 1.722, 95% CI = 1.192-2.488, P = 0.004). The C allele carriers had lower TC, low-density lipoprotein cholesterol, apolipoprotein (Apo) A1 and ApoB levels than the C allele non-carriers after atorvastatin treatment. Stratified analysis showed that the DNAH11 rs12670798 may interact with the gender, age, body mass index, cigarette smoking, and alcohol consumption to affect the risk of CHD and IS. The DNAH11 rs12670798 variant was associated with elevated serum TC levels, and increased risk of CHD and IS in the Chinese Han population. The C allele carriers had higher serum TC levels and the risk of CHD and IS than the C allele non-carriers, but they had lower TC, LDL-C, ApoA1 and ApoB levels than the C allele non-carriers after atorvastatin treatment.

Project description:BackgroundLittle is known about the association of the dedicator of cytokinesis 7 (DOCK7 rs1748195) and angiopoietin like 3 (ANGPTL3 rs12563308) single nucleotide polymorphisms (SNPs) and their haplotypes with serum lipid levels and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese populations. This study aimed to detect such association in a Southern Chinese Han population.MethodsThis study included 1728 subjects (CAD, 568; IS, 539; and controls, 621). Genotypes of the two SNPs were determined by the Snapshot technology.ResultsThe genotypic and allelic frequencies of the rs1748195 SNP were different between CAD patients and controls (P < 0.05 for each), the rs1748195G allele frequency was higher in CAD patients than in controls (27.6% vs. 23.6%, P = 0.024). The genotypic frequencies of the rs12563308 SNP were also different between CAD patients and controls (P = 0.021). The rs1748195 SNP was associated with an increased risk of CAD after controlling for potential confounders and Bonferroni correction (P < 0.025 considered statistically significant; Recessive: OR = 1.79, 95% CI = 1.04-3.06, P = 0.017; Log-additive: OR = 1.27, 95% CI = 1.02-1.57, P = 0.014), whereas the rs12563308 SNP was associated with a decreased risk of CAD (Dominant: OR = 0.69, 95% CI = 0.45-0.94, P = 0.011; Log-additive: OR = 0.73, 95% CI = 0.49-0.89, P = 0.009). The rs1748195 SNP was also associated with an increased risk of severity to coronary artery atherosclerosis (Dominant: OR = 1.45, 95% CI = 1.07-2.11, P = 0.017; Log-additive: OR = 1.35, 95% CI = 1.09-1.82, P = 0.013). The interactions of SNP-environment on serum lipid levels and the risk of severity to coronary artery atherosclerosis, CAD and IS were noted. The rs1748195G-rs12563308T haplotype was associated with an increased angiographic severity to coronary artery atherosclerosis (OR = 1.46, 95% CI = 1.05-2.03), and the risk of CAD (OR = 1.37, 95% CI = 1.08-1.74). The interactions of haplotype-hypertension on the risk of CAD and haplotype-drinking on the risk of CAD/IS were observed.ConclusionsThese results suggest that the DOCK-ANGPTL3 SNPs and their haplotypes were associated with the angiographic severity to coronary artery atherosclerosis and the risk of CAD and IS in the Southern Chinese Han population.

Dataset Information

The association between the DNAH11 rs10248618 SNP and serum lipid traits, the risk of coronary artery disease, and ischemic stroke.

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The association between the <i>DNAH11</i> rs10248618 SNP and serum lipid traits, the risk of coronary artery disease, and ischemic stroke.

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