Zhang Meihong, Yuan Hongying, Li Changsheng, Li Chunling
Department of Traditional Chinese Medicine in Liaocheng City People's Hospital, Liaocheng, China.
Nephron. 2017;135(3):224-230. doi: 10.1159/000450656. Epub 2016 Dec 24.
Several studies have focused on the association between peroxisome proliferators-activated receptor gamma (PPARG) polymorphism and diabetic nephropathy (DN); however, the results of these studies were inconsistent, and until now, no population-based study has focused on the impact of PPARG gene-abdominal obesity interaction on DN risk. The aim of this study was to investigate the impact of PPARG polymorphisms and its interaction with abdominal obesity on DN risk in the Chinese Han population.
A total of 848 patients with type 2 diabetes mellitus, including 420 DN patients and 428 controls were recruited. Generalized multifactor dimensionality reduction (GMDR) and logistic regression model were used to examine the association and interaction between single nucleotide polymorphism and abdominal obesity on DN; OR and 95% CI were calculated.
We found a significant association between CG or GG in rs1805192 and increased DN risk. DN risk was higher in the carriers of CG or GG genotype of rs1805192 than those with CC genotype; OR (95% CI) was 1.31 (1.11-1.58). GMDR analysis suggested a significant 2-locus model (p = 0.0107) involving rs1805192 and abdominal obesity, indicating a potential gene-environment interaction between rs1805192 and abdominal obesity. Overall, the 2-locus models had a cross-validation consistency of 10 of 10, and the testing accuracy of 62.17%.
Our results support an important association between rs1805192 minor allele (G allele) of PPARG and increased DN risk; the interaction analysis showed a combined effect of interaction between rs1805192 and abdominal obesity on DN risk. The results obtained from this study are meaningful for studies on individualized PPARG agonist in treating DN for different persons, such as abdominal obese or non-abdominal obese subject.
多项研究聚焦于过氧化物酶体增殖物激活受体γ（PPARG）基因多态性与糖尿病肾病（DN）之间的关联；然而，这些研究结果并不一致，且迄今为止，尚无基于人群的研究关注PPARG基因与腹型肥胖的相互作用对DN风险的影响。本研究旨在探讨PPARG基因多态性及其与腹型肥胖的相互作用对中国汉族人群DN风险的影响。
共纳入848例2型糖尿病患者，其中420例为DN患者，428例为对照。采用广义多因素降维法（GMDR）和逻辑回归模型来检验单核苷酸多态性与腹型肥胖对DN的关联及相互作用；计算比值比（OR）和95%置信区间（CI）。
我们发现rs1805192位点的CG或GG与DN风险增加显著相关。rs1805192位点CG或GG基因型携带者的DN风险高于CC基因型者；OR（95%CI）为(1.31(1.11 - １.58))。GMDR分析提示存在一个涉及rs1805192和腹型肥胖的显著两位点模型（p = 0.0107），表明rs1805192与腹型肥胖之间存在潜在的基因-环境相互作用。总体而言，两位点模型的交叉验证一致性为10/10，检验准确性为62.17%。
我们的结果支持PPARG的rs1805192次要等位基因（G等位基因）与DN风险增加之间存在重要关联；相互作用分析显示rs1805192与腹型肥胖的相互作用对DN风险具有联合效应。本研究结果对于针对不同人群（如腹型肥胖或非腹型肥胖个体）治疗DN的个体化PPARG激动剂研究具有重要意义。
