2 型糖尿病（T2D）相关基因、父母 T2D 病史和肥胖对 T2D 发病影响的性别差异：一项病例对照研究。

Sex differences in the influence of type 2 diabetes (T2D)-related genes, parental history of T2D, and obesity on T2D development: a case-control study.

机构信息

Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Cuauhtémoc, 06720, Ciudad de Mexico, México.

Instituto Nacional de Medicina Genómica, Ciudad de Mexico, México.

出版信息

Biol Sex Differ. 2023 Jun 8;14(1):39. doi: 10.1186/s13293-023-00521-y.

DOI:10.1186/s13293-023-00521-y

PMID:37291636

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10251612/

Abstract

BACKGROUND

This study investigated the effect of sex and age at type 2 diabetes (T2D) diagnosis on the influence of T2D-related genes, parental history of T2D, and obesity on T2D development.

METHODS

In this case-control study, 1012 T2D cases and 1008 healthy subjects were selected from the Diabetes in Mexico Study database. Participants were stratified by sex and age at T2D diagnosis (early, ≤ 45 years; late, ≥ 46 years). Sixty-nine T2D-associated single nucleotide polymorphisms were explored and the percentage contribution (R) of T2D-related genes, parental history of T2D, and obesity (body mass index [BMI] and waist-hip ratio [WHR]) on T2D development was calculated using univariate and multivariate logistic regression models.

RESULTS

T2D-related genes influenced T2D development most in males who were diagnosed early (R = 23.5%; females, R = 13.5%; males and females diagnosed late, R = 11.9% and R = 7.3%, respectively). With an early diagnosis, insulin production-related genes were more influential in males (76.0% of R) while peripheral insulin resistance-associated genes were more influential in females (52.3% of R). With a late diagnosis, insulin production-related genes from chromosome region 11p15.5 notably influenced males while peripheral insulin resistance and genes associated with inflammation and other processes notably influenced females. Influence of parental history was higher among those diagnosed early (males, 19.9%; females, 17.5%) versus late (males, 6.4%; females, 5,3%). Unilateral maternal T2D history was more influential than paternal T2D history. BMI influenced T2D development for all, while WHR exclusively influenced males.

CONCLUSIONS

The influence of T2D-related genes, maternal T2D history, and fat distribution on T2D development was greater in males than females.

摘要

背景

本研究旨在探讨 2 型糖尿病（T2D）发病时的性别和年龄对 T2D 相关基因、父母 T2D 病史和肥胖对 T2D 发病的影响。

方法

在这项病例对照研究中，我们从糖尿病墨西哥研究数据库中选择了 1012 例 T2D 病例和 1008 例健康对照。根据 T2D 发病时的性别和年龄（早发，≤45 岁；晚发，≥46 岁）进行分层。共探讨了 69 个与 T2D 相关的单核苷酸多态性，采用单变量和多变量逻辑回归模型计算 T2D 相关基因、父母 T2D 病史和肥胖（体重指数 [BMI] 和腰臀比 [WHR]）对 T2D 发病的贡献率（R）。

结果

在早发 T2D 的男性中，T2D 相关基因对 T2D 发病的影响最大（R=23.5%；女性 R=13.5%；晚发的男性和女性 R=11.9%和 R=7.3%）。早发 T2D 时，胰岛素分泌相关基因在男性中更为重要（R=76.0%），而外周胰岛素抵抗相关基因在女性中更为重要（R=52.3%）。晚发 T2D 时，染色体 11p15.5 区域的胰岛素分泌相关基因对男性有显著影响，而外周胰岛素抵抗以及与炎症和其他过程相关的基因对女性有显著影响。早发 T2D 者的父母 T2D 病史影响更大（男性 19.9%；女性 17.5%），而晚发 T2D 者的影响较小（男性 6.4%；女性 5.3%）。单侧母亲 T2D 病史比单侧父亲 T2D 病史更有影响。BMI 对所有人群的 T2D 发病均有影响，而 WHR 仅对男性有影响。