Dab2 基因遗传多态性与中国维吾尔族 2 型糖尿病的相关性研究。
Genetic polymorphism of the Dab2 gene and its association with Type 2 Diabetes Mellitus in the Chinese Uyghur population.
机构信息
State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
出版信息
PeerJ. 2023 Jun 21;11:e15536. doi: 10.7717/peerj.15536. eCollection 2023.
OBJECTIVE
The human Disabled-2 (Dab2) protein is an endocytic adaptor protein, which plays an essential role in endocytosis of transmembrane cargo, including low-density lipoprotein cholesterol (LDL-C). As a candidate gene for dyslipidemia, Dab2 is also involved in the development of type 2 diabetes mellitus(T2DM). The aim of this study was to investigate the effects of genetic variants of the Dab2 gene on the related risk of T2DM in the Uygur and Han populations of Xinjiang, China.
METHODS
A total of 2,157 age- and sex-matched individuals (528 T2DM patients and 1,629 controls) were included in this case-control study. Four high frequency SNPs (rs1050903, rs2255280, rs2855512 and rs11959928) of the Dab2 gene were genotyped using an improved multiplex ligation detection reaction (iMLDR) genotyping assay, and the forecast value of the SNP for T2DM was assessed by statistical analysis of clinical data profiles and gene frequencies.
RESULTS
We found that in the Uygur population studied, for both rs2255280 and rs2855512, there were significant differences in the distribution of genotypes (AA/CA/CC), and the recessive model (CC CA + AA) between T2DM patients and the controls ( < 0.05). After adjusting for confounders, the recessive model (CC CA + AA) of both rs2255280 and rs2855512 remained significantly associated with T2DM in this population (rs2255280: OR = 5.303, 95% CI [1.236 to -22.755], = 0.025; rs2855512: OR = 4.892, 95% CI [1.136 to -21.013], = 0.033). The genotypes (AA/CA/CC) and recessive models (CC CA + AA) of rs2855512 and rs2255280 were also associated with the plasma glucose and HbA1c levels (all < 0.05) in this population. There were no significant differences in genotypes, all genetic models, or allele frequencies between the T2DM and control group in the Han population group (all > 0.05).
CONCLUSIONS
The present study suggests that the variation of the Dab2 gene loci rs2255280 and rs2855512 is related to the incidence of T2DM in the Uygur population, but not in the Han population. In this study, these variations in Dab2 were an independent predictor for T2DM in the Uygur population of Xinjiang, China.
目的
人类Disabled-2（Dab2）蛋白是一种内吞衔接蛋白，在跨膜货物（包括低密度脂蛋白胆固醇[LDL-C]）的内吞作用中发挥重要作用。作为血脂异常的候选基因，Dab2也参与了 2 型糖尿病（T2DM）的发生。本研究旨在探讨中国新疆维吾尔族和汉族人群中 Dab2 基因的遗传变异与 T2DM 相关的风险。
方法
本病例对照研究共纳入 2157 名年龄和性别匹配的个体（528 名 T2DM 患者和 1629 名对照）。使用改良多重连接检测反应（iMLDR）基因分型检测方法对 Dab2 基因的 4 个高频单核苷酸多态性（rs1050903、rs2255280、rs2855512 和 rs11959928）进行基因分型，并通过对临床数据谱和基因频率的统计分析评估 SNP 对 T2DM 的预测价值。
结果
我们发现，在研究的维吾尔族人群中，rs2255280 和 rs2855512 的基因型（AA/CA/CC）和隐性模型（CC CA + AA）分布存在显著差异（ < 0.05）。在调整混杂因素后，这两个 SNP 的隐性模型（CC CA + AA）在该人群中与 T2DM 仍显著相关（rs2255280：OR = 5.303，95%CI [1.236 至 -22.755]， = 0.025；rs2855512：OR = 4.892，95%CI [1.136 至 -21.013]， = 0.033）。rs2855512 和 rs2255280 的隐性模型（CC CA + AA）和基因型（AA/CA/CC）也与该人群的血浆葡萄糖和 HbA1c 水平相关（均 < 0.05）。在汉族人群中，T2DM 患者和对照组之间的基因型、所有遗传模型或等位基因频率均无显著差异（均 > 0.05）。
结论
本研究表明，Dab2 基因座 rs2255280 和 rs2855512 的变异与维吾尔族人群 T2DM 的发病有关，但与汉族人群无关。在本研究中，Dab2 的这些变异在中国新疆维吾尔族人群中是 T2DM 的独立预测因子。
Zotero 插件