Single-nucleotide polymorphisms of peroxisome proliferator-activated receptor-γ are associated with systemic lupus erythematosus in a Chinese Han population.

Abstract

Evidence has indicated that peroxisome-proliferator activated receptor-γ (PPAR-γ) agonists could be used in the prevention and treatment of murine systemic lupus erythematosus (SLE). However, to our knowledge, just one previous study has focused on the association between PPAR-γ polymorphisms and SLE in humans. To investigate the association between PPAR-γ polymorphisms and SLE in a Chinese population and on additional gene-gene interaction between multiple single nucleotide polymorphisms (SNPs) in PPAR-γ. Three SNPs of PPAR-γ were selected for genotyping in this case-control study: rs1805192, rs10865710 and rs709158. Logistic regression was used to examine the association between the three SNPs and SLE, and the odds ratio (OR) and 95% CI were calculated. Generalized multifactor dimensionality reduction (GMDR) was used to investigate additional interaction. All genotypes were distributed according to Hardy-Weinberg equilibrium. Logistic regression analysis showed a significant association between genotypes of rs1805192 variants and decreased SLE risk, after adjustment for sex, age, smoking, high-fat diet, low-fibre diet, alcohol status, body mass index and waist circumference. Participants with Ala allesles had a lower SLE risk than those homozygous for the wild-type allele (OR=0.78; 95% CI 0.69-0.92). GMDR analysis indicated that there was a significant two-locus model (P=0.001) involving rs1805192 and rs10865710, indicating a potential gene-gene interaction between them. Overall, the two-locus models had a cross-validation consistency of 10 out of 10 and a testing accuracy of 60.72%. There was a significant association between PPAR-γ rs1805192 genotypes and decreased SLE risk, and a potential gene-gene interaction between rs1805192 and rs10865710.