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,Wu-Xian Chen,Rui-Xing Yin,Xiao-Li Cao,Jin-Zhen Wu,Feng Huang

doi:10.18632/oncotarget.20349

Liu Miao, Wu-Xian Chen + Show 4 more

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https://doi.org/10.18632/oncotarget.20349

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Abstract

AimThis 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.MethodsGenotyping 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.ResultsThe 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.ConclusionSeveral 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.

Highlights

Coronary heart disease (CHD) and ischemic stroke (IS) are the most prevalent geriatric diseases and the major determinant of mortality and morbidity worldwide [13]
The rs3759387 SNP was associated with the risk of CHD and IS in different genetic models
Several SNPs interacted with alcohol consumption and cigarette smoking to increase serum high-density lipoprotein cholesterol (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

Summary

Introduction

Coronary heart disease (CHD) and ischemic stroke (IS) are the most prevalent geriatric diseases and the major determinant of mortality and morbidity worldwide [13]. As a complex and multifactorial disorder, CHD and IS are resulted from lots of pathogenic factors, including genetic factors and environmental exposures [5]. The major pathological basis of these two diseases had proved to be atherosclerosis which the essential as an ambitious inflammatory disorder. Both of diseases would be participated in the same genetic and environmental backgrounds, including gender, time to life, hypercholesterol, hypertension, diabetes, cigarette smoking, and genetic factors [6,7,8,9]. Some genetic variants that were initially shown to have an effect on the risk of CHD were detected to be related to IS soon afterwards [12, 13]

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