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TNF-α 启动子多态性与 2 型糖尿病遗传易感性的关联研究:中国汉族人群的横断面研究。

Investigations of associations between TNF-α promoter polymorphisms and genetic susceptibility to type 2 diabetes mellitus: A cross-sectional study in Chinese Han population.

机构信息

Department of Endocrinology, The Affiliated Hospital of Yunnan University & The Second People's Hospital of Yunnan Province, Kunming, Yunnan, China.

Postgraduate Division, Kunming Medical University, Kunming, Yunnan, China.

出版信息

Int J Immunogenet. 2024 Dec;51(6):388-396. doi: 10.1111/iji.12698. Epub 2024 Oct 10.

DOI:10.1111/iji.12698
PMID:39387337
Abstract

Type 2 diabetes (T2DM) is characterised by insulin resistance and a relative shortage of insulin secretion. Tumour necrosis factor-α (TNF-α) plays an important role in insulin resistance by impairing insulin signal transduction. The variants of the TNF-α promoter region are considered to influence its transcription and are associated with the TNF-α level. Therefore, it is worth detecting the association of the variants in the TNF-α gene with the development of T2DM. The aim of this study was to investigate the association of five variants (rs1799964, rs1800630, rs1799724, rs1800629 and rs361525) in the TNF-α gene promoter region with T2DM in a Chinese Han population. A total of 713 subjects with T2DM and 751 nondiabetic subjects were genotyped using the TaqMan method. The associations of the five variants with the development of T2DM were evaluated. The associations of the five variant genotypes with metabolic traits in nondiabetic subjects were analysed. Our data showed that the A allele of rs1800629 could increase the risk of developing T2DM (p = .002, OR = 1.563; 95% CI: 1.18-2.08). According to inheritance mode analysis, compared with the G/G genotype, the G/A+2A/A genotype of rs1800629 showed a risk effect on T2DM in the log-additive mode (p = .002, OR = 1.56; 95% CI: 1.17-2.07). The haplotypes analysis identified that the rs1799724-rs1800629CA was associated with high risk of the development of T2DM (p = .002, OR = 1.559, 95% CI: 1.173-2.072). Conversely, the rs1799724-rs1800629CG was a protective haplotype of T2DM (p = .001, OR = 0.732, 95% CI: 0.607-0.884). Moreover, compared with the rs1799964 (T/T+C/T) genotype, the rs1799964 C/C genotype was associated with higher glycosylated haemoglobin (HbA1c) levels in nondiabetic subjects (p = .017). Our results revealed that the rs1800629 in the TNF-α gene promoter region was associated with T2DM in a Chinese Han population.

摘要

2 型糖尿病(T2DM)的特征是胰岛素抵抗和相对胰岛素分泌不足。肿瘤坏死因子-α(TNF-α)通过损害胰岛素信号转导在胰岛素抵抗中起重要作用。TNF-α 启动子区域的变异被认为会影响其转录,并与 TNF-α 水平相关。因此,检测 TNF-α 基因中变异与 T2DM 发展之间的关联是值得的。本研究旨在探讨 TNF-α 基因启动子区域中五个变异(rs1799964、rs1800630、rs1799724、rs1800629 和 rs361525)与中国汉族人群 T2DM 发病的相关性。采用 TaqMan 法对 713 例 T2DM 患者和 751 例非糖尿病患者进行基因分型。评估了五个变体与 T2DM 发病的相关性。分析了非糖尿病患者中五个变体基因型与代谢特征的相关性。我们的数据表明,rs1800629 的 A 等位基因可能增加 T2DM 的发病风险(p =.002,OR = 1.563;95%CI:1.18-2.08)。根据遗传模式分析,与 G/G 基因型相比,rs1800629 的 G/A+2A/A 基因型在加性模式下对 T2DM 具有风险效应(p =.002,OR = 1.56;95%CI:1.17-2.07)。单体型分析表明,rs1799724-rs1800629CA 与 T2DM 发病风险相关(p =.002,OR = 1.559,95%CI:1.173-2.072)。相反,rs1799724-rs1800629CG 是 T2DM 的保护性单体型(p =.001,OR = 0.732,95%CI:0.607-0.884)。此外,与 rs1799964(T/T+C/T)基因型相比,rs1799964C/C 基因型与非糖尿病患者的糖化血红蛋白(HbA1c)水平升高相关(p =.017)。我们的结果表明,TNF-α 基因启动子区域的 rs1800629 与中国汉族人群的 T2DM 相关。

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