中国人群中 CYP2C8 和 CYP2C9 的多态性与 2 型糖尿病易感性的关系

IF 1 Q4 GENETICS & HEREDITY Gene Reports Pub Date : 2024-10-02 DOI:10.1016/j.genrep.2024.102053

Wensu Wang , Li Jin , Jianguo Shen , Yi Zhang , Rong Zhang

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引用次数: 0

摘要

目的CYP2C8 和 CYP2C9 是细胞色素 P450 环氧酶，负责将花生四烯酸代谢为环二十碳三烯酸（EETs）。这些 EETs 作为脂质介质在 2 型糖尿病（T2DM）中发挥着至关重要的作用，具有多种有益功效。本研究旨在调查中国人群中 CYP2C8 和 CYP2C9 基因变异与 T2DM 的关系。方法我们根据 HapMap 中国和日本数据对 CYP2C8 中的 9 个标记单核苷酸多态性 (SNP) 和 CYP2C9 中的 10 个标记 SNP 进行了基因分型。随后，我们在由 3410 名 T2DM 患者和 3401 名健康对照者组成的中国队列中对这些 SNP 进行了基因分型。结果在我们的研究人群中，我们发现位于 CYP2C9 基因区的 rs1819173 与 T2DM 显著相关。值得注意的是，A 等位基因的存在对 T2DM 有保护作用，其几率比为 0.840（95 % 置信区间：0.780-0.904，P = 3.04 × 10-6）。此外，涉及 CYP2C8 中 rs2071426 和 rs6583967 的特定单倍型（GT 和 AT）与 T2DM 有关联（P = 0.049 和 0.038）。随后，我们对 rs1819173 与非酒精性脂肪肝（NAFLD）之间的相关性进行了分析，结果显示两者之间存在显著相关性（OR = 0.764，95 % CI：0.629-0.928，P = 0.007）。

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Association of polymorphisms in CYP2C8 and CYP2C9 with susceptibility to type 2 diabetes mellitus in a Chinese population

Aims

CYP2C8 and CYP2C9 are cytochrome P450 epoxygenases responsible for metabolizing arachidonic acid into epoxyeicosatrienoic acids (EETs). These EETs play a crucial role as lipid mediators with numerous beneficial effects in type 2 diabetes mellitus (T2DM). In this study, we aimed to investigate the association of CYP2C8 and CYP2C9 genetic variants with T2DM in a Chinese population.

Methods

We conducted genotyping for 9 tag single nucleotide polymorphisms (SNPs) in CYP2C8 and 10 tag SNPs in CYP2C9 based on HapMap Chinese and Japanese data. Subsequently, we genotyped these SNPs in a Chinese cohort comprising 3410 individuals with T2DM and 3401 healthy controls. Statistical analyses were performed to assess the association between these SNPs and T2DM.

Results

In our study population, we observed that rs1819173, located within the CYP2C9 gene region, was significantly associated with T2DM. Notably, the presence of the A allele was found to be protective against T2DM, as indicated by an odds ratio of 0.840 (95 % confidence interval: 0.780–0.904, P = 3.04 × 10⁻⁶). Furthermore, specific haplotypes (GT and AT) involving rs2071426 and rs6583967 in CYP2C8 exhibited associations with T2DM (P = 0.049 and 0.038, respectively). Subsequently, we conducted an analysis of the association between rs1819173 and non-alcoholic fatty liver disease (NAFLD), revealing a significant correlation (OR = 0.764, 95 % CI: 0.629–0.928, P = 0.007).

Conclusion

Our research identified a genetic variants rs1819173 within CYP2C8 are significantly associated with T2DM susceptibility in the Chinese population.

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.