Genetic polymorphism of the Dab2 gene and its association with Type 2 Diabetes Mellitus in the Chinese Uyghur population.
Genetic polymorphism of the Dab2 gene and its association with Type 2 Diabetes Mellitus in the Chinese Uyghur population.
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作者：
Li YP;Adi D;Wang YH;Wang YT;Li XL;Fu ZY;Liu F;Aizezi A;Abuzhalihan J;Gai M;Ma X;Li XM;Xie X;Ma Y
人Disabled-2（Dab2）蛋白是一种内吞衔接蛋白，其在跨膜货物（包括低密度脂蛋白胆固醇（LDL-C））的内吞中起重要作用。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。本研究的目的是探讨Dab2基因的遗传变异对中国新疆维吾尔族和汉族人群中2型糖尿病相关风险的影响。本病例对照研究共纳入2,157名年龄和性别匹配的个体（528名T2DM患者和1,629名对照）。采用改良的多重连接检测反应（iMLDR）基因分型方法对Dab2基因的4个高频SNP（rs1050903、rs2255280、rs2855512和rs11959928）进行分型，并通过统计分析临床资料和基因频率，评估SNP对T2DM的预测价值。结果发现，在维吾尔族人群中，rs2255280和rs2855512的基因型（AA/CA/CC）和隐性模式（CC vs. CA + AA）在T2DM患者和对照组中的分布差异均有统计学意义（P <0.05）。调整混杂因素后，隐性模型在该人群中，rs2255280和rs2855512（CC vs. CA + AA）均与T2DM显著相关（rs2255280：OR = 5.303，95%CI [1.236至-22.755]，P = 0.025; rs2855512：OR = 4.892，95%CI [1.136至-21.013]，P = 0.033）。rs2855512和rs2255280基因型（AA/CA/CC）和隐性模式（CC vs. CA + AA）与该人群血糖和HbA1c水平相关（均P <0.05）。汉族T2DM组与对照组的基因型、各遗传模型及等位基因频率差异均无统计学意义（均P> 0.05）。提示Dab2基因位点rs2255280和rs2855512的变异与维吾尔族T2DM的发病有关，而与汉族T2DM的发病无关。在这项研究中，Dab2的这些变异是中国新疆维吾尔族人群中T2DM的独立预测因子。
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. 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. 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 vs. CA + AA) between T2DM patients and the controls (P < 0.05). After adjusting for confounders, the recessive model (CC vs. 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], P = 0.025; rs2855512: OR = 4.892, 95% CI [1.136 to −21.013], P = 0.033). The genotypes (AA/CA/CC) and recessive models (CC vs. CA + AA) of rs2855512 and rs2255280 were also associated with the plasma glucose and HbA1c levels (all P < 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 P > 0.05). 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.
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影响因子：
120.7
作者：
Besseling, Joost;Kastelein, John J. P.;Hovingh, G. Kees
通讯作者：
Hovingh, G. Kees
DOI：
10.1016/s1470-2045(14)71116-7
发表时间：
2015-04
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Balachandran VP;Gonen M;Smith JJ;DeMatteo RP
通讯作者：
DeMatteo RP
影响因子：
168.9
作者：
McCrimmon, Rory J.;Ryan, Christopher M.;Frier, Brian M.
通讯作者：
Frier, Brian M.
影响因子：
3.4
作者：
Lu, Mingjun;Xu, Lingling;Chen, Tao
通讯作者：
Chen, Tao
影响因子：
6.6
作者：
Lv, Jianping;Ren, Hui;Mei, Songli
通讯作者：
Mei, Songli