单核苷酸多态性及其单倍型、基因-基因和基因-环境相互作用与血脂异常的关系。
Associations between SNPs, their haplotypes, gene-gene, and gene-environment interactions and dyslipidemia.
机构信息
Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China.
Guangxi Key Laboratory Base of Precision Medicine in Cardio-Cerebrovascular Disease Control and Prevention, Nanning 530021, Guangxi, People's Republic of China.
出版信息
Aging (Albany NY). 2021 Feb 17;13(4):5906-5927. doi: 10.18632/aging.202514.
In this study, we investigated associations between single nucleotide polymorphisms (SNPs) in the tubulin beta class I () and WW domain-containing oxidoreductase () genes, gene-gene interactions, and gene-environment interactions and dyslipidemia in the Chinese Maonan ethnic group. Four SNPs (rs3132584, rs3130685, rs2222896, and rs2548861) were genotyped in unrelated subjects with normal lipid levels (864) or dyslipidemia (1129). While 5.0% of Maonan subjects carried the rs3132584TT genotype, none of the Chinese Han in Beijing subjects did. Allele and genotype frequencies differed between the normal and dyslipidemia groups for three SNPs (rs3132584, rs3130685, and rs2222896). rs2222896G allele carriers in the normal group had higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol levels. The rs3132584GG, rs3130685CC+TT, and rs2222896GG genotypes as well as the rs2222896G-rs2548861G and rs2222896G-rs2548861T haplotypes were associated with an elevated risk of dyslipidemia; the rs2222896A-rs2548861T and rs2222896A-rs2548861G haplotypes were associated with a reduced risk of dyslipidemia. Among the thirteen interaction types identified, rs3132584T-rs3130685T-rs2222896G-rs2548861T increased the risk of dyslipidemia 1.371-fold. Fourteen two- to four-locus optimal interactive models for SNP-SNP, haplotype-haplotype, gene-gene, and gene-environment interactions exhibited synergistic or contrasting effects on dyslipidemia. Finally, the interaction between rs3132584 and rs2222896 increased the risk of dyslipidemia 2.548-fold and predicted hypertension.
在这项研究中,我们调查了 tubulin beta 类 I () 和 WW 结构域含有氧化还原酶 () 基因中的单核苷酸多态性 (SNPs) 与血脂异常的相关性,以及基因-基因相互作用、基因-环境相互作用与血脂异常的相关性。在血脂正常的无关个体(864 例)和血脂异常的个体(1129 例)中,对 4 个 SNP(rs3132584、rs3130685、rs2222896 和 rs2548861)进行了基因分型。然而,5.0%的毛南族个体携带 rs3132584TT 基因型,而北京汉族人群中没有。在正常组和血脂异常组中,三个 SNP(rs3132584、rs3130685 和 rs2222896)的等位基因和基因型频率存在差异。正常组 rs2222896G 等位基因携带者的低密度脂蛋白胆固醇水平较高,高密度脂蛋白胆固醇水平较低。rs3132584GG、rs3130685CC+TT、rs2222896GG 基因型以及 rs2222896G-rs2548861G 和 rs2222896G-rs2548861T 单倍型与血脂异常风险升高相关;rs2222896A-rs2548861T 和 rs2222896A-rs2548861G 单倍型与血脂异常风险降低相关。在确定的 13 种 相互作用类型中,rs3132584T-rs3130685T-rs2222896G-rs2548861T 使血脂异常的风险增加 1.371 倍。14 个二至四个位点最佳交互模型用于 SNP-SNP、单倍型-单倍型、基因-基因和基因-环境相互作用,对血脂异常具有协同或相反的影响。最后,rs3132584 与 rs2222896 的相互作用使血脂异常的风险增加了 2.548 倍,并预测了高血压。