Liang J, Zhu Y, Liu X-K, Qiu Q-Q, Sun Y-T, Wang Y, Pei Y, Yang M-Q, Qi L
Department of Endocrinology and Central Laboratory, Xuzhou Central Hospital, Jiangsu, China.
Xuzhou Clinical School of Xuzhou Medical College, Affiliated Hospital of Southeast University, Xuzhou, Jiangsu, China.
Exp Clin Endocrinol Diabetes. 2018 Sep;126(9):540-545. doi: 10.1055/s-0042-109607. Epub 2018 Jun 22.
Obesity is strongly associated with insulin resistance and elevated plasma glucose levels. The rs9356744 polymorphism in the gene is associated with body mass index (BMI) only in East Asians. Here, we examined the effect of the rs9356744 polymorphism on glucose-related traits and prediabetes in Chinese adults.
A total of 2 357 participants were enrolled from the Cardiometabolic Risk in Chinese (CRC) Study, including 499 persons with prediabetes, 204 persons with type 2 diabetes, and 1 654 normoglycemic controls. The rs9356744 polymorphism in was genotyped and analyzed in all participants.
Despite the positive relationship between obesity and glucose traits, the T allele of rs9356744, which is associated with a predisposition to obesity, was correlated with lower levels of 2-h oral glucose tolerance test (OGTT) plasma glucose (2hPG) (β=- 0.2104 and =0.0233), glycated hemoglobin (HbA1c) (β=- 0.0551 and =0.0298) and higher levels of homeostasis model of assessment β-cell function (HOMA-B) (β=5.282 and =0.0424). After further adjustment for BMI, the levels of HOMA-B maintained a similar increased trend across rs9356744 genotype (β=3.277 and =0.1958). In stratified analyses, the associations of rs9356744 with 2hPG and HbA1c were significant for individuals with a low BMI. Moreover, an antagonism action of BMI and rs9356744 on 2hPG ( for interaction=0.0055) was observed. In addition, we found a protective effect of rs9356744 on prediabetes.
The rs9356744 T allele associated with a predisposition to obesity showed a protective effect on HbA1c, 2hPG, and prediabetes. BMI was mediator of the association between the genetic variant and HbA1c, 2hPG, and prediabetes.
肥胖与胰岛素抵抗及血糖水平升高密切相关。该基因中的rs9356744多态性仅在东亚人群中与体重指数（BMI）相关。在此，我们研究了rs9356744多态性对中国成年人血糖相关特征及糖尿病前期的影响。
从中国心脏代谢风险（CRC）研究中招募了2357名参与者，包括499名糖尿病前期患者、204名2型糖尿病患者和1654名血糖正常的对照者。对所有参与者进行该基因中rs9356744多态性的基因分型和分析。
尽管肥胖与血糖特征之间存在正相关，但与肥胖易感性相关的rs9356744的T等位基因与2小时口服葡萄糖耐量试验（OGTT）血浆葡萄糖（2hPG）水平较低（β=-0.2104，P=0.0233）、糖化血红蛋白（HbA1c）水平较低（β=-0.0551，P=0.0298）以及稳态模型评估β细胞功能（HOMA-B）水平较高（β=5.282，P=0.0424）相关。在进一步调整BMI后，HOMA-B水平在rs9356744基因型中保持相似的升高趋势（β=3.277，P=0.1958）。在分层分析中，rs9356744与2hPG和HbA1c的关联在低BMI个体中显著。此外，观察到BMI与rs9356744对2hPG存在拮抗作用（交互作用P=0.0055）。另外，我们发现rs9356744对糖尿病前期有保护作用。
与肥胖易感性相关的rs9356744 T等位基因对HbA1c、2hPG和糖尿病前期具有保护作用。BMI是该基因变异与HbA1c、2hPG和糖尿病前期之间关联的中介因素。
