DGAT2-MOGAT2 SNPs and Gene-Environment Interactions on Serum Lipid Profiles and the Risk of Ischemic Stroke

Background: The genetic susceptibility to ischemic stroke (IS) is still not well-understood. Recent genome-wide association studies (GWASes) found that several single nucleotide polymorphisms (SNPs) in the Diacylglycerol acyltransferase 2 gene (DGAT2) and monoacylglycerol O-acyltransferase 2 (MOGAT2...

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Autores principales:	Yong-Gang Zhou, Rui-Xing Yin, Feng Huang, Jin-Zhen Wu, Wu-Xian Chen, Xiao-Li Cao
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	diacylglycerol acyltransferase 2 gene monoacylglycerol O-acyltransferase 2 gene single nucleotide polymorphisms ischemic stroke serum lipid levels interaction Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/cc9b86495e314ce9b1b1ef5620e20e14
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spelling	oai:doaj.org-article:cc9b86495e314ce9b1b1ef5620e20e142021-11-30T18:04:32ZDGAT2-MOGAT2 SNPs and Gene-Environment Interactions on Serum Lipid Profiles and the Risk of Ischemic Stroke2297-055X10.3389/fcvm.2021.685970https://doaj.org/article/cc9b86495e314ce9b1b1ef5620e20e142021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.685970/fullhttps://doaj.org/toc/2297-055XBackground: The genetic susceptibility to ischemic stroke (IS) is still not well-understood. Recent genome-wide association studies (GWASes) found that several single nucleotide polymorphisms (SNPs) in the Diacylglycerol acyltransferase 2 gene (DGAT2) and monoacylglycerol O-acyltransferase 2 (MOGAT2) cluster were associated with serum lipid levels. However, the association between the DGAT2-MOGAT2 SNPs and serum lipid phenotypes has not yet been verified in the Chinese people. Therefore, the present study was to determine the DGAT2-MOGAT2 SNPs and gene-environment interactions on serum lipid profiles and the risk of IS.Methods: Genotyping of 5 SNPs (DGAT2 rs11236530, DGAT2 rs3060, MOGAT2 rs600626, MOGAT2 rs609379, and MOGAT2 rs10899104) in 544 IS patients and 561 healthy controls was performed by the next-generation sequencing technologies. The association between genotypes and serum lipid data was determined by analysis of covariance, and a corrected P-value was adopted after Bonferroni correction. Unconditional logistic regression analysis was performed to assess the association between genotypes and the risk of IS after adjustment of potential confounders.Results: The rs11236530A allele was associated with increased risk of IS (CA/AA vs. CC, OR = 1.45, 95%CI = 1.12–1.88, P = 0.0044), whereas the rs600626G-rs609379A-rs10899104G haplotype was associated with decreased risk of IS (adjusted OR = 0.67, 95% CI = 0.48–0.93, P = 0.018). The rs11236530A allele carriers had lower high-density lipoprotein cholesterol (HDL-C) concentrations than the rs11236530A allele non-carriers (P < 0.001). The interactions of rs11236530-smoking, rs3060-smoking and rs10899104-smoking influenced serum apolipoprotein B levels, whereas the interactions of rs11236530- and rs3060-alcohol affected serum HDL-C levels (PI < 0.004–0.001). The interaction of rs600626G-rs609379A-rs10899104G-alcohol (OR = 0.41, 95% CI = 0.22–0.76) and rs600626G-rs609379C-rs10899104T-alcohol (OR = 0.12, 95% CI = 0.04–0.36) decreased the risk of IS (PI < 0.0001).Conclusions: The rs11236530A allele was associated with decreased serum HDL-C levels in controls and increased risk of IS in patient group. The rs600626G-rs609379A-rs10899104G haplotype, the rs600626G-rs 609379A-rs10899104G-alcohol and rs600626G-rs609379C-rs10899104T-alcohol interactions were associated with decreased risk of IS. The rs11236530 SNP may be a genetic marker for IS in our study populations.Yong-Gang ZhouRui-Xing YinFeng HuangJin-Zhen WuWu-Xian ChenXiao-Li CaoFrontiers Media S.A.articlediacylglycerol acyltransferase 2 genemonoacylglycerol O-acyltransferase 2 genesingle nucleotide polymorphismsischemic strokeserum lipid levelsinteractionDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	diacylglycerol acyltransferase 2 gene monoacylglycerol O-acyltransferase 2 gene single nucleotide polymorphisms ischemic stroke serum lipid levels interaction Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	diacylglycerol acyltransferase 2 gene monoacylglycerol O-acyltransferase 2 gene single nucleotide polymorphisms ischemic stroke serum lipid levels interaction Diseases of the circulatory (Cardiovascular) system RC666-701 Yong-Gang Zhou Rui-Xing Yin Feng Huang Jin-Zhen Wu Wu-Xian Chen Xiao-Li Cao DGAT2-MOGAT2 SNPs and Gene-Environment Interactions on Serum Lipid Profiles and the Risk of Ischemic Stroke
description	Background: The genetic susceptibility to ischemic stroke (IS) is still not well-understood. Recent genome-wide association studies (GWASes) found that several single nucleotide polymorphisms (SNPs) in the Diacylglycerol acyltransferase 2 gene (DGAT2) and monoacylglycerol O-acyltransferase 2 (MOGAT2) cluster were associated with serum lipid levels. However, the association between the DGAT2-MOGAT2 SNPs and serum lipid phenotypes has not yet been verified in the Chinese people. Therefore, the present study was to determine the DGAT2-MOGAT2 SNPs and gene-environment interactions on serum lipid profiles and the risk of IS.Methods: Genotyping of 5 SNPs (DGAT2 rs11236530, DGAT2 rs3060, MOGAT2 rs600626, MOGAT2 rs609379, and MOGAT2 rs10899104) in 544 IS patients and 561 healthy controls was performed by the next-generation sequencing technologies. The association between genotypes and serum lipid data was determined by analysis of covariance, and a corrected P-value was adopted after Bonferroni correction. Unconditional logistic regression analysis was performed to assess the association between genotypes and the risk of IS after adjustment of potential confounders.Results: The rs11236530A allele was associated with increased risk of IS (CA/AA vs. CC, OR = 1.45, 95%CI = 1.12–1.88, P = 0.0044), whereas the rs600626G-rs609379A-rs10899104G haplotype was associated with decreased risk of IS (adjusted OR = 0.67, 95% CI = 0.48–0.93, P = 0.018). The rs11236530A allele carriers had lower high-density lipoprotein cholesterol (HDL-C) concentrations than the rs11236530A allele non-carriers (P < 0.001). The interactions of rs11236530-smoking, rs3060-smoking and rs10899104-smoking influenced serum apolipoprotein B levels, whereas the interactions of rs11236530- and rs3060-alcohol affected serum HDL-C levels (PI < 0.004–0.001). The interaction of rs600626G-rs609379A-rs10899104G-alcohol (OR = 0.41, 95% CI = 0.22–0.76) and rs600626G-rs609379C-rs10899104T-alcohol (OR = 0.12, 95% CI = 0.04–0.36) decreased the risk of IS (PI < 0.0001).Conclusions: The rs11236530A allele was associated with decreased serum HDL-C levels in controls and increased risk of IS in patient group. The rs600626G-rs609379A-rs10899104G haplotype, the rs600626G-rs 609379A-rs10899104G-alcohol and rs600626G-rs609379C-rs10899104T-alcohol interactions were associated with decreased risk of IS. The rs11236530 SNP may be a genetic marker for IS in our study populations.
format	article
author	Yong-Gang Zhou Rui-Xing Yin Feng Huang Jin-Zhen Wu Wu-Xian Chen Xiao-Li Cao
author_facet	Yong-Gang Zhou Rui-Xing Yin Feng Huang Jin-Zhen Wu Wu-Xian Chen Xiao-Li Cao
author_sort	Yong-Gang Zhou
title	DGAT2-MOGAT2 SNPs and Gene-Environment Interactions on Serum Lipid Profiles and the Risk of Ischemic Stroke
title_short	DGAT2-MOGAT2 SNPs and Gene-Environment Interactions on Serum Lipid Profiles and the Risk of Ischemic Stroke
title_full	DGAT2-MOGAT2 SNPs and Gene-Environment Interactions on Serum Lipid Profiles and the Risk of Ischemic Stroke
title_fullStr	DGAT2-MOGAT2 SNPs and Gene-Environment Interactions on Serum Lipid Profiles and the Risk of Ischemic Stroke
title_full_unstemmed	DGAT2-MOGAT2 SNPs and Gene-Environment Interactions on Serum Lipid Profiles and the Risk of Ischemic Stroke
title_sort	dgat2-mogat2 snps and gene-environment interactions on serum lipid profiles and the risk of ischemic stroke
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/cc9b86495e314ce9b1b1ef5620e20e14
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DGAT2-MOGAT2 SNPs and Gene-Environment Interactions on Serum Lipid Profiles and the Risk of Ischemic Stroke

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