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中国人群中rs7903146(C/T)多态性与2型糖尿病的关联:临床特征与种族背景

Association of rs7903146 (C/T) Polymorphism with Type 2 Diabetes Mellitus in a Chinese Population: Clinical Characteristics and Ethnic Context.

作者信息

Lu Yung-Chuan, Yu Teng-Hung, Hsuan Chin-Feng, Hsu Chia-Chang, Hung Wei-Chin, Wang Chao-Ping, Tang Wei-Hua, Cheng Min-Chih, Chung Fu-Mei, Lee Yau-Jiunn, Lee Thung-Lip

机构信息

Division of Endocrinology and Metabolism, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung 82445, Taiwan.

Division of Cardiology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung 82445, Taiwan.

出版信息

Diagnostics (Basel). 2025 Aug 21;15(16):2110. doi: 10.3390/diagnostics15162110.

Abstract

: The () rs7903146 polymorphism has been strongly associated with type 2 diabetes mellitus (T2DM) in various populations; however, its impact on different ethnic groups is not fully understood. Given the distinct minor allele frequency in Chinese populations, this study aimed to analyze the association of rs7903146 with the risk of T2DM in a Han Chinese cohort and its relationship with relevant clinical parameters. : We conducted a case-control study including 600 patients with type 2 diabetes mellitus (T2DM) and 511 sex-matched non-diabetic controls of Han Chinese descent. The rs7903146 (C/T) polymorphism was genotyped using a TaqMan™ SNP assay. Clinical parameters, including body mass index (BMI), fasting plasma glucose, hemoglobin A1c, lipid profile, and high-sensitivity C-reactive protein (hs-CRP), were compared between genotypes. Logistic regression analyses were performed under a dominant genetic model (CT/TT vs. CC), adjusting for age, sex, systolic and diastolic blood pressure, BMI, and smoking status. Subgroup analyses were conducted by sex, BMI category, age at diagnosis, and family history of T2DM. Given the exploratory nature of this study and the low frequency of the TT genotype, no formal correction for multiple testing was applied. : Frequencies of the CT and TT genotypes were higher in the diabetic group ( = 0.045) and were significantly associated with an increased risk of T2DM under a dominant genetic model (adjusted OR = 2.24, = 0.025). Individuals with CT/TT genotypes had elevated fasting glucose and hs-CRP levels; these genotypes were also linked to higher BMI in the female T2DM patients. The T allele frequency varied across ethnic groups, being lowest in East Asians and highest in Latin (Brazilian/mixed ancestry) populations. Mechanistically, the T allele may contribute to T2DM via altered expression, impaired insulin secretion, inflammation, and metabolic dysregulation. : The rs7903146 T allele was associated with an increased risk of T2DM and higher fasting glucose and hs-CRP levels in this Han Chinese cohort. The CT/TT genotypes were also associated with higher BMI in the female T2DM patients. While the findings are consistent with the known effects of this variant in other populations, mechanistic hypotheses such as the involvement of inflammatory or metabolic pathways remain hypothetical and warrant further functional validation.

摘要

rs7903146多态性在不同人群中与2型糖尿病(T2DM)密切相关;然而,其对不同种族群体的影响尚未完全明确。鉴于该位点在中国人群中次要等位基因频率的差异,本研究旨在分析rs7903146与中国汉族人群T2DM发病风险的相关性及其与相关临床参数的关系。我们开展了一项病例对照研究,纳入600例2型糖尿病(T2DM)患者和511例性别匹配的非糖尿病汉族对照。采用TaqMan™ SNP检测法对rs7903146(C/T)多态性进行基因分型。比较各基因型间的临床参数,包括体重指数(BMI)、空腹血糖、糖化血红蛋白、血脂谱和高敏C反应蛋白(hs-CRP)。在显性遗传模型(CT/TT与CC)下进行逻辑回归分析,并对年龄、性别、收缩压和舒张压、BMI及吸烟状况进行校正。按性别、BMI分类、诊断时年龄和T2DM家族史进行亚组分析。鉴于本研究的探索性及TT基因型的低频率,未进行多重检验的正式校正。糖尿病组中CT和TT基因型的频率较高(P = 0.045),在显性遗传模型下与T2DM发病风险增加显著相关(校正OR = 2.24,P = 0.025)。CT/TT基因型个体的空腹血糖和hs-CRP水平升高;在女性T2DM患者中,这些基因型还与较高的BMI相关。T等位基因频率在不同种族群体中有所差异,在东亚人群中最低,在拉丁(巴西/混合血统)人群中最高。从机制上讲,T等位基因可能通过改变基因表达、损害胰岛素分泌、引发炎症和代谢失调导致T2DM。在这个中国汉族队列中,rs7903146 T等位基因与T2DM发病风险增加以及较高的空腹血糖和hs-CRP水平相关。CT/TT基因型在女性T2DM患者中也与较高的BMI相关。虽然这些发现与该变异在其他人群中的已知作用一致,但诸如炎症或代谢途径参与等机制假说仍属推测,有待进一步的功能验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6664/12385235/3188086c165b/diagnostics-15-02110-g001.jpg

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