Functional polymorphisms of the APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster are associated with dyslipidemia in a sex-specific pattern
Functional polymorphisms of the APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster are associated with dyslipidemia in a sex-specific pattern
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DOI：
10.7717/peerj.6175
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发表时间：
2019-01-04
期刊：
影响因子：
2.7
通讯作者：
Wu, Yanhua
中科院分区：
文献类型：
--
作者：
Bai, Wei;Kou, Changgui;Wu, Yanhua
背景：血脂异常会增加许多疾病的风险，包括中风、心血管疾病和代谢相关疾病。先前的研究表明，单核苷酸多态性（SNP）与不同的血脂水平相关。因此，本研究探讨了中国东北地区总样本人群中APOA1/C3/A4/A5-ZPR1-BUD13基因簇基因多态性与血脂异常之间的关系。方法：纳入中国吉林省的3,850名受试者，并测量其血脂水平。使用聚合酶链式反应和 MALDI-TOF-MS 对 6 个功能性 SNP（APOA1 rs5072、APOC3 rs5128、APOA4 rs5104、APOA5 rs651821、ZPR1 rs2075294 和 BUD13 rs10488698）进行基因分型。采用Logistic回归分析探讨APOA1/C3/A4/A5-ZPR1-BUD13基因簇基因多态性与血脂异常的关系。利用SNPStats程序和Haploview软件进行连锁不平衡和单倍型分析。结果：所有SNPs均符合Hardy-Weinberg平衡。 Logistic回归分析显示，在整个组中，rs5072、rs5128和rs651821与高甘油三酯血症相关，rs5104和rs651821与低HDL胆固醇血症相关。 rs651821 与男性和女性组中的高甘油三酯血症和低 HDL 胆固醇血症相关。然而，在女性中，rs5072被发现与高甘油三酯血症相关。单倍型分析显示单倍型TGCCGC和CAGCGC与总体、男性和女性群体的血脂异常相关。结论：APOA1/C3/A4/A5-ZPR1-BUD13基因簇中的SNP与血脂异常相关。此外，该基因簇中的 APOA1 rs5072 与血脂异常的关联在性别之间存在差异。因此，需要更多的研究来证实这一结论，并且这些结果背后的机制值得进一步探索。
Background: Dyslipidemia contributes to the risk of many diseases, including stroke, cardiovascular disease and metabolic-related diseases. Previous studies have indicated that single nucleotide polymorphisms (SNPs) are associated with different levels of serum lipid. Therefore, this study explored the relationship between the APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster gene polymorphisms and dyslipidemia in the total sample population and stratified by genders in a northeast Chinese population.Methods: A total of 3,850 participants from Jilin Province, China, were enrolled in our study, and their serum lipid levels were measured. Six functional SNPs (APOA1 rs5072, APOC3 rs5128, APOA4 rs5104, APOA5 rs651821, ZPR1 rs2075294 and BUD13 rs10488698) were genotyped using polymerase chain reaction and MALDI-TOF-MS. Logistic regression analysis was performed to explore the relationship of APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster gene polymorphisms with dyslipidemia. Linkage disequilibrium and haplotype analyses were performed with the SNPStats program and Haploview software.Results: All SNPs conformed to Hardy-Weinberg equilibrium. Logistic regression analysis revealed that rs5072, rs5128 and rs651821 were associated with hypertriglyceridemia, rs5104 and rs651821 were associated with low-HDL cholesterolemia in overall group. rs651821 was associated with hypertriglyceridemia and low-HDL cholesterolemia in both the male and female group. However, among females, rs5072 was observed to be associated with hypertriglyceridemia. Haplotype analysis showed that haplotypes TGCCGC and CAGCGC were associated with dyslipidemia in the overall, male and female groups.Conclusion: SNPs in the APOA1/C3/A4/A5-ZPR1-BUD13 gene cluster were associated with dyslipidemia. Furthermore, the association of APOA1 rs5072 in this gene cluster with dyslipidemia differed between genders; thus, additional studies are needed to confirm this conclusion, and the mechanisms underlying these results warrant further exploration.