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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

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 s...

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Autores principales: Miao, Liu, Yin, Rui-Xing, Huang, Feng, Chen, Wu-Xian, Cao, Xiao-Li, Wu, Jin-Zhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641170/
https://www.ncbi.nlm.nih.gov/pubmed/29069827
http://dx.doi.org/10.18632/oncotarget.20349
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author Miao, Liu
Yin, Rui-Xing
Huang, Feng
Chen, Wu-Xian
Cao, Xiao-Li
Wu, Jin-Zhen
author_facet Miao, Liu
Yin, Rui-Xing
Huang, Feng
Chen, Wu-Xian
Cao, Xiao-Li
Wu, Jin-Zhen
author_sort Miao, Liu
collection PubMed
description 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.
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spelling pubmed-56411702017-10-24 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 Miao, Liu Yin, Rui-Xing Huang, Feng Chen, Wu-Xian Cao, Xiao-Li Wu, Jin-Zhen Oncotarget Research Paper 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. Impact Journals LLC 2017-08-18 /pmc/articles/PMC5641170/ /pubmed/29069827 http://dx.doi.org/10.18632/oncotarget.20349 Text en Copyright: © 2017 Miao et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Miao, Liu
Yin, Rui-Xing
Huang, Feng
Chen, Wu-Xian
Cao, Xiao-Li
Wu, Jin-Zhen
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641170/
https://www.ncbi.nlm.nih.gov/pubmed/29069827
http://dx.doi.org/10.18632/oncotarget.20349
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