Association Of The Adiponectin Gene (ADIPOQ)+45T> G Polymorphism With Metabolic Syndrome Among Han Chinese In Liangshan, Sichuan Province Of China

Background and significanceThe metabolic syndrome (MS) is a cluster of abnormalities characterized by obesity, impaired glucose metabolism, hypertension or elevated blood pressure, and dyslipidemia. MS is associated with the development of type2diabetes mellitus and of cardiovascular disease. Adiponectin has been reported to be independently associated with MS. It is a relatively abundant serum protein secreted by adipocytes. Some studies showed that the level of adiponectin is correlated with insulin resistance, and with glucose and lipid metabolism. Adiponectin gene (ADIPOQ) is located on human chromosome3q27, which was showed containing the type2diabetes mellitus and metabolic syndrome susceptibility gene by genome-wide scan. The+45T> G polymorphism is one of the most common variants of the exon2of the ADIPOQ gene and it is reported to be associated with serum levels of adiponectin, insulin sensitivity, obesity and T2DM. However, whether the+45T> G polymorphism is associated with MS still remains unclear. Previous studies showed a low prevalence of hypertension among Yi farmers in remote mountainous areas of southwestern China where the largest Yi community is located. In addition, Wang et al reported that the age-and sex-adjusted prevalence of MS was9.9times higher in Yi migrants (23.8%) and6.3times higher in Han people (15.2%) than in Yi farmers (2.4%) and assumed, therefore, lifestyle strongly influenced development of MS in Han and Yi Chinese. In addition, MS is a complex disease impacted both by environmental and genetic factors. This study was therefore designed to examine the possible association of the ADIPOQ+45T> G polymorphism and related influence factors with MS in citizens among Han Chinese in Sichuan province of China to further explore the mechanisms that may affect MS and provide reference for the prevention of MS in Han Chinese.ObjectivesThis study was designed to examine the possible association of the adiponectin gene (ADIPOQ)+45T> G polymorphism and related influence factors with the metabolic syndrome, and the gene-environment interactions to MS in citizens among Han Chinese in liangshan, Sichuan province of China.MethodsUsing stratified multistage cluster sampling method, a cross-sectional survey was conducted among Han citizens living in Xichang city and Butuo, Zhaojue, Jinyang, Puge, Puluo, Xide counties, in Sichuan province in the year of2007-2008. Questionnaire survey, anthropometric measurement and blood test were carried out. A case-control design was used including120patients with the metabolic syndrome and120unrelated controls, matched on age and gender. Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) technique was used to analyze single nucleotide polymorphism (ADIPOQ+45T> G polymorphism) between cases and controls.Continuous variables are presented as means±standard deviation (SD) and difference between the cases and controls was compared using Student’s t-test for normally-distributed variables or non-parametric Mann-Whitney Latest for non-normally-distributed ones. Test for Hardy-Weinberg equilibrium and comparison of allele and genotype distribution between MS cases and controls were assessed by chi-square test. Odds ratios (OR) and their95%confidence intervals (CI) were calculated using the Mantel-Haenszel method. Multiple logistic regression analysis was performed to estimate an association of the+45T> G polymorphism and environment factors with the risk of MS. All data analyses were performed using SAS version9.2software (SAS Institute Inc., Cary, NC, USA).ResultsEducation was a protective factor of metabolic syndrome (OR=0.455,95%CI:0.232-0.892, P=0.022), while family history of related diseases was a risk factor of metabolic syndrome (OR=3.258,95%CI:1.706-6.223,P=0.0003).Frequencies of the genotype were in Hardy-Weinberg equilibrium in controls. Frequencies of the TT, TG and GG genotypes were61.2%,34.5%and4.3%in the cases, and70.4%,25.9%and3.7%in the controls, respectively. Compared with TT, there was no difference in distribution of the TG, GG and (TG+GG) genotypic frequencies between cases and controls. In addition, no difference was observed in frequency of allele between the two groups. Results of multiple logistic regression analysis showed that the ADIPOQ+45T> G polymorphism was an independent risk factor for MS. After adjustment for education, physical activity, family history of related diseases, smoking and drinking, carriers of the G allele (TG+GG) had a1.882-fold higher risk for developing MS (OR=1.882,95%CI:1.031-3.435, P=0.039) than subjects with TT genotype.The ADIPOQ+45T> G polymorphism (TT vs. TG+GG) drinking interaction was significantly associated with MS (OR=4.274,95%CI:1.470-12.425, P=0.008). Synergy index beween the ADIPOQ+45T> G polymorphism and drinking was1.73attributable proportion due to interaction was32.3%, pure attributable proportion due to ineraction was42.2%, relative excess risk of interaction was1.38.ConclusionsAmong Han Chinese in Sichuan province of China, education was a protective factor of metabolic syndrome, while family history of related diseases was a risk factor of metabolic syndrome. The association between the ADIPOQ+45T> G polymorphism and MS was independent of multiple confounders. The ADIPOQ+45T> G polymorphism and drinking showed a positive interaction to MS.