Interaction between peroxisome proliferator-activated receptor gamma polymorphism and obesity on type 2 diabetes in a Chinese Han population

Lv et al. Diabetol Metab Syndr (2017) 9:7 DOI 10.1186/s13098-017-0205-5 Diabetology & Metabolic Syndrome Open Access RESEARCH Interaction between peroxisome proliferator‑activated receptor gamma polymorphism and obesity on type 2 diabetes in a Chinese Han population Xiaohui Lv1†, Li Zhang1†, Jiayu Sun1, Zhigang Cai1, Qing Gu1, Ruipeng Zhang2 and Aiyun Shan1* Abstract Aims: The aim of this study was to investigate the association of four single nucleotide polymorphisms (SNPs) of peroxisome proliferator-activated receptor gamma (PPARG) with type 2 diabetes mellitus (T2DM) risk and additional role of gene-obesity interaction. Methods: Four SNPs were selected for genotyping in the case–control study: rs1805192, rs709158, rs3856806 and rs4684847. Generalized multifactor dimensionality reduction (GMDR) model and logistic regression was used to examine the interaction between SNP and obesity on T2DM, odds ratio (OR) and 95% confident interval (95% CI) were calculated. Results: T2DM risk was significantly higher in individuals with rs1805192-G allele (p < 0.05). The carriers of G allele of the rs1805192 polymorphism revealed increased T2DM risk than those with CC variants (CG + GG versus CC, adjusted OR (95% CI) 1.76 (1.45–2.06), p < 0.001). T2DM risk was also significantly higher in individuals with rs3856806-T allele (p < 0.05). The carriers of T allele of the rs3856806 polymorphism revealed increased T2DM risk than those with CC variants (CT + TT versus CC, adjusted OR (95% CI) 1.25 (1.17–1.76), p < 0.001). There was a significant two-locus model (p = 0.0107) involving rs1805192 and obesity. Obese subjects with CG or GG genotype have the highest T2DM risk, compared to subjects with CC genotype and normal BMI (OR 2.40, 95% CI 1.68–3.63). Conclusions: Our results support an important association between rs1805192 and rs3856806 minor allele (G allele) of PPARG and increased T2DM risk, the interaction analysis shown a combined effect of G- obesity interaction between rs1805192 and obesity on increased T2DM risk. Keywords: Type 2 diabetes mellitus, PPAR, Polymorphism, Obesity, Interaction Background Diabetes mellitus (DM) is a group of common metabolic disorders that share the phenotype of hyperglycemia. Globally, about 5.4% of adult population has been estimated to have type 2 diabetes mellitus (T2DM) [1]. Several types of diabetes mellitus exist and are caused by a *Correspondence: † Xiaohui Lv and Li Zhang contributed equally to this work 1 Shenzhen Futian District Traditional Chinese Medicine Hospital, No. 6001 in North Central Avenue, Futian District, Shenzhen 518033, Guangdong, China Full list of author information is available at the end of the article complex interaction of genetics and environmental factors [2]. Type 2 diabetes has a strong genetic component. There is evidence that the Pro12Ala polymorphism is linked to obesity and T2DM [3]. The peroxisome proliferator-activated receptor gamma (PPARG) is now recognized to play a main PPARG entered the spotlight as a major player in metabolic regulation in the early 1990s [4] through the discovery of thiazolidinediones (TZDs) as potent synthetic insulin-sensitizing drugs. TZDs quickly passed clinical trials and became front-line agents in the treatment of type II diabetes for their robust insulin-sensitizing and © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Lv et al. Diabetol Metab Syndr (2017) 9:7 glucose-lowering actions, although their popularity has recently decreased in response to safety concerns. Activation of PPARG results in systemic insulin sensitization through complex mechanisms involving multiple. PPARG was the first gene reproducibly associated with T2DM. The association between the substitution of alanine by proline at codon 12 of PPARG2 (Ala12 allele) and the risk for T2DM has been widely studied since Yen et al. [5], first reported this polymorphism. Some studies indicated that rs1805192 SNP plays a key role in regulating the expression of numerous genes involved in lipid metabolism, metabolic syndrome, inflammation, and atherosclerosis [6, 7]. Some environmental risk factors for T2DM were suggested, such as obesity, which was reported in different populations [8–10]. However, till now, no study focused on the impact of gene- environment interaction between PPARG and obesity on T2DM risk in Chinese population. So the aim of this study was to investigate the association of PPARG, and additional PPARG gene- obesity interaction with T2DM risk based on a Chinese population. Methods Subjects This was a case–control study. Chinese patients with T2DM were consecutively recruited between January 2012 and December 2013 from the Shenzhen Futian District traditional Chinese medicine hospital. A total of 1297 subjects consist of 647 T2DM patients and 650 normal controls were included in this study, including 606 males and 691 females. The mean age of all subjects was 54.3 ± 15.8 years old. The selected subjects were similar to those who were not selected in terms of age, sex, smoking status and alcohol consumption. Informed consent was obtained from all participants. Body measurements Data on general demographic information and lifestyle information for all participants were obtained using a standard questionnaire administered by trained staffs. Body weight, height and waist circumference (WC) was measured, and body mass index (BMI) was calculated as weight in kilograms divided by the square of the height in meters. Cigarette smokers were those who self-reported smoking cigarettes at least once a day for 1 year or more [11]. Alcohol consumption was expressed as the sum of milliliters of alcohol per week from wine, beer, and spirits [12]. Blood samples were collected in the morning after at least 8 h of fasting. All plasma and serum samples were frozen at −80 °C until laboratory testing. Plasma glucose was measured using an oxidase enzymatic method. Concentrations of high-density lipoprotein (HDL)-cholesterol and triglyceride (TG) were assessed enzymatically Page 2 of 6 by an automatic biochemistry analyzer (Hitachi Inc, Tokyo, Japan) using commercial reagents. All analysis was performed by the same lab. Genomic DNA extraction and genotyping We selected SNPs within PPARG according to the following methods: (1) more studied SNPs, such as rs1805192, which was more studied in previous studies; (2) we also selected the others SNP of PPARG, in order to find new SN (...truncated)