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

// Liu Miao 1 , Rui-Xing Yin 1 , Feng Huang 1 , Wu-Xian Chen 1 , Xiao-Li Cao 2 and Jin-Zhen Wu 1 1 Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China 2 Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China Correspondence to: Rui-Xing Yin, email: yinruixing@163.com 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/m 2 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.