Oncotarget

Research Papers:

The effect of MVK-MMAB variants, their haplotypes and G×E interactions on serum lipid levels and the risk of coronary heart disease and ischemic stroke

Liu Miao, Rui-Xing Yin _, Feng Huang, Wu-Xian Chen, Xiao-Li Cao and Jin-Zhen Wu

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Oncotarget. 2017; 8:72801-72817. https://doi.org/10.18632/oncotarget.20349

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Abstract

Liu Miao1, Rui-Xing Yin1, Feng Huang1, Wu-Xian Chen1, Xiao-Li Cao2 and Jin-Zhen Wu1

1Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China

2Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China

Correspondence to:

Rui-Xing Yin, email: [email protected]

Keywords: mevalonate kinase, methylmalonic aciduria (cobalamin deficiency) cblB type, single nucleotide polymorphism, coronary heart disease and ischemic stroke, lipids and interaction

Received: March 27, 2017    Accepted: July 04, 2017    Published: August 18, 2017

ABSTRACT

Aim: This study aimed to detect the association of the mevalonate kinase (MVK) and methylmalonic aciduria (cobalamin deficiency) cblB type (MMAB) gene variants, their haplotypes, and gene-environment (G×E) interactions on serum lipid levels and the risk of coronary heart disease (CHD) and ischemic stroke (IS) in a Chinese Han population.

Methods: Genotyping of the rs3759387, rs7134594, rs877710 and rs9593 SNPs in 846 CHD and 869 IS patients and 847 healthy controls was performed by PCR-RFLP and Sanger sequencing. Logistic regression and factor regression were used to investigate the association of 4 MVK-MMAB SNPs and serum lipid levels and the risk of CHD and IS.

Results: The genotypic and allelic frequencies of the rs3759387 and rs7134594 SNPs differed between controls and patients (P < 0.0125-0.001). The rs3759387 SNP was associated with the risk of CHD and IS in different genetic models. The A-T-G-A and C-T-C-T haplotypes were associated with increased risk of CHD. The haplotype of A-T-G-A was associated with an increased risk of IS, whereas the C-T-G-A haplotype was associated with a decreased risk of IS. Interactions of C-T-C-T-smoking or C-T-C-T-age on the risk of CHD, and A-T-G-A-hypertension or A-T-G-A-age on the risk of IS were also observed. The subjects with the rs3759387AA genotype in controls had lower high-density lipoprotein cholesterol (HDL-C) levels than did the subjects with AC/CC genotypes. Several SNPs interacted with alcohol consumption and cigarette smoking to increase serum HDL-C and apolipoprotein A1 levels, but they interacted with body mass index ≥ 24 kg/m2 to decrease serum HDL-C and apolipoprotein A1 levels.

Conclusion: Several MVK-MMAB variants, especially the rs3759387 SNP, 4 main haplotypes, and G×E interactions were associated with serum lipid levels and the risk of CHD and IS in a Chinese Han population.


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