| ObjectiveThe objective of this study was to explore the association between the polymorphism of five sites in janus kinase-2(JAK2) gene and obesity, and explain the role of gene-environmental interaction in the generation of obesity.MethodIn this study, a total of 1921 resident rural subjects aged 18-74 years from the Rural Diabetes, Obesity and Lifestyle Study(Rural Diab) were recruited by simple random sampling method. The normal weighted, overweighted, obese subjects accounted for 35.40%(680), 40.05%(779), 25.05%(462) of total sample size,respectively. Individual data was collected by face to face survey and anthropometric measurements were performed. Fasting blood samples were collected. The fasting plasma glucose and lipid spectrum were measured by automatic biochemical analyzer.The whole blood genomic DNA was extracted by magnetic beads method. The genotypes of five locis in JAK2 gene were detected by Taqman fluorescence probe method. The software of Epidata3.1 was used for data double entry. All data analysis was conducted using SAS9.1. Odds ratios(OR) and 95% confidence interval(95% CI)adjusted for potential covariates were evaluated by unconditioned logistic regression model. Combined effects of the five sites were evaluated by genetic risk score model.Haplo.stats in R was applied to assess among haplotype between five sites. The gene-environmental interaction was evaluated by Multifactor Dimensionality Reduction software(MDR) and logistic regression model.Results1. The results of the association between JAK2 gene and the obesity related traits showed that there were significant differences in WHR and WHt R among participants with different genotype of rs3780378(P<0.05). WC, WHR, WHt R and TG were significantly different in each group of rs7847294(P<0.05). Significant differences of WC, WHR, WHt R, BMI, TC and TG were found in different genotypes forrs2230724(P<0.05). For rs2149556, significant difference in TC was also discovered in different genotypes(P<0.05).2. Compared with individuals with wild type genotype, individuals with heterozygote were at higher risk of overweight for rs7847294(OR=1.376, 95%CI:1.086-1.743) and rs2230724(OR=1.496, 95%CI: 1.104-2.027) by adjusting age,gender, smoking, alcohol consumption, high fat diet, fruits and vegetables intake and physical activity factors.3. The frequency of the haplotype TCTAC is 0.337. Individuals with TCTGC haplotype were at a higher risk of obesity(OR=1.066, 95%CI: 1.004-1.288)compared with individuals with TCTAC haplotype by adjusting gender, smoking,alcohol consumption, high fat diet, fruits and vegetables intake and physical activity factors.4. The results of weighted genetic risk score(WGRS) showed that the risk of being obesity in the second quarters group and the highest group was 1.381 and 1.610 times as much as that in the lowest score group, respectively. In addition, significant difference of BMI and WC were found in different score groups(P<0.05).5. The analysis of gene-environmental interaction and obesity analysis suggested that individuals with(GG+AG) gene type and high fat diet were at higher risk of overweight or obesity(OR=1.066, 95%CI: 1.004-1.288) compared with subjects with AA gene type and normal diet.ConclusionRs7847294 and rs2230724 in JAK2 gene are associated with overweight. JAK2 gene SNP haplotype and weighted genetic risk score are associated with the risk of overweight and obesity. There is significantly interaction between rs2230724 and high fat diet in the generation of obesity. |
