Nested Case-control Study Of The Effect Of Genetic Polymorphism Of Peroxisome Proliferator-activated Receptors On Metabolic Syndrome And Its Components

Objective1. To explore the association between genetic polymorphism of peroxisome proliferator-activated receptors ( PPARs ) and metabolic syndrome (MS) and its components.2. To discuss the gene-gene interaction during the genetic polymorphism of PPARs subtypes and the effect on MS.Methods1. Based on the MS cohort study in Jiangsu Province, 1:1 matched nested case-control study was used to analyze the genetic polymorphisms of PPARs in 820 subjects. Ten sites of PPARs subtypes were selected.Polymerase chain reaction restriction fragment length polymorphism was used to detect the genetic polymorphisms of rs4253778 while other sites were detected by Taqman fluorescence probe method.2. Conditional logistic regression was used to analyze association between PPARs and MS and its components.3. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the interaction among different gene sites.Results1. The genetic polymorphism of rs2016520 and rs10865710 were significantly associated with onset of MS. The OR for carring rs2016520 C alleles and rs10865710 G alleles to develop MS were 0.67 (95% CI: 0.51-0.89) and 1.33 (95% CI: 1.02-1.75), respectively. After adjusted for smoking, alcohol consumption, high fat diet, low fiber diet and professional physical activity and other genes sites, OR for rs2016520 and rs10865710 was 0.64 (95% CI: 0.48-0.86) and 1.31 (95% CI: 1.02-1.74).2. During the rest sites of PPARs, rs1800206 site V alleles carriers had significantly increased high TG and low HDL-C incidence, the OR were 2.87 (95% CI: 1.96-4.21) and 1.45 (95% CI: 1.01-2.08). Rs4684847 site T alleles carrier had significantly increased HBP incidence,and OR was 1.37 (95% CI: 1.02-1.85). Rs3856806 site T alleles carriers had significantly increased high TG incidence, and OR was 1.39 (95% CI: 1.02-1.90).3. There is an interaction among rs135539, rs2016520, rs3856806, rs709158, rs1805192, rs4684847 and rs10865710 in GMDR model, and it is the best model.Conclusion1. The polymorphism of two sites in PPARs directly influences the onset of MS, the rest of sites influence different aspects of the body metabolism. PPARs play an important role in regulation of lipid metabolism, obesity and high blood pressure.2. There is an interactions among PPARα, PPARδand PPARγ. The multiple agonists of PPARs may had more efficience in the treatment of metabolic disorders.