PI3K/AKT/mTOR通路基因变异与中国2型糖尿病的关联
Association of PI3K/AKT/mTOR pathway genetic variants with type 2 diabetes mellitus in Chinese.
作者信息
Yin Xueyao, Xu Zhiye, Zhang Ziyi, Li Lin, Pan Qianqian, Zheng Fenping, Li Hong
机构信息
Department of Endocrinology, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, PR China.
Department of Endocrinology, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, PR China.
出版信息
Diabetes Res Clin Pract. 2017 Jun;128:127-135. doi: 10.1016/j.diabres.2017.04.002. Epub 2017 Apr 10.
AIMS
Genetic variations in the PI3K/AKT/mTOR signaling pathway may be associated with an increasing risk of obesity and diabetes. In this study, we aimed to test whether polymorphisms in the PIK3CA (catalytic subunit of PI3K), AKT1, AKT2, and FRAP1 (mTOR) genes were associated with the risk of type 2 diabetes mellitus (T2DM) among Chinese population.
METHODS
A case-control study was conducted and included 248 cases with T2DM and 101 controls. A total of 28 tagSNPs from the 4 genes were chosen based on HapMap datasets and these were genotyped using a MassARRAY Compact Analyzer.
RESULTS
Individuals carrying the rs2494746 CG/GG or rs2494738GA/GG genotype in AKT1 had a higher risk of T2DM, compared with those carrying homozygous variants (adjusted OR=1.79, 95% CI: 1.05-3.05, P=0.03 for rs2494746; adjusted OR=1.58, 95% CI: 1.19-2.10, P=0.02 for rs2494738). Furthermore, we found that haplotype GC in the AKT1 gene comprised rs2494738 and rs3803304, indicating a significant association with T2DM (OR=1.08, 95% CI: 1.01-1.15, P=0.03). Finally, generalized multifactor dimensionality reduction (GMDR) analysis indicated that the best interactive model included 3 polymorphisms: rs2494746 (AKT1), rs4802071 (AKT2), and rs4845856 (FRAP1).
CONCLUSIONS
Our study suggests that PI3K/AKT/mTOR pathway genes may participate in the development of T2DM.
目的
PI3K/AKT/mTOR信号通路中的基因变异可能与肥胖和糖尿病风险增加相关。在本研究中，我们旨在检测PIK3CA（PI3K催化亚基）、AKT1、AKT2和FRAP1（mTOR）基因的多态性是否与中国人群2型糖尿病（T2DM）风险相关。
方法
进行了一项病例对照研究，纳入248例T2DM患者和101例对照。基于HapMap数据集从这4个基因中选择了总共28个标签单核苷酸多态性（tagSNP），并使用MassARRAY Compact Analyzer对其进行基因分型。
结果
与携带纯合变异的个体相比，携带AKT1基因rs2494746 CG/GG或rs2494738 GA/GG基因型的个体患T2DM的风险更高（rs2494746的校正比值比[OR]=1.79，95%置信区间[CI]：1.05 - 3.05，P = 0.03；rs2494738的校正OR = 1.58，95% CI：1.19 - 2.10，P = 0.02）。此外，我们发现AKT1基因中由rs2494738和rs3803304组成的单倍型GC与T2DM存在显著关联（OR = 1.08，95% CI：1.01 - 1.15，P = 0.03）。最后，广义多因素降维（GMDR）分析表明，最佳交互模型包括3个多态性：rs2494746（AKT1）、rs4802071（AKT2）和rs4845856（FRAP1）。
结论
我们的研究表明PI3K/AKT/mTOR通路基因可能参与T2DM的发生发展。
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