Association Study On SNPs Of Toll Like Receptor 9 Gene And Environmental Factors With Systemic Lupus Erythematosus In Anhui Han Population

Objective To explore frequencies and polymorphisms distrbution of the exon 2 and the promoter region of TLR9 gene, and analyze the susceptibility to systemic lupus erythematosus (SLE) of Han ethnics in Anhui Province of eastern China, and to analyze the influences of interaction of many environmental factors and gene-enviromental on systemic lupus erythematosus.Methods A total of 77 patients with SLE from 74 nuclear families, aged from 12 to 63 years, were enrolled according to 1997 criteria of American College of Rheumatology (ACR), 211 family members of these patients were also included. Genotyping was performed by PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) Assay. Family-based association analysis was performed to explore the association between gene polymorphism and SLE. And the possible interactions between gene and environment on SLE were analyzed with conditional logistic regression method.Results Among 77 patients with SLE, the CC, CT and TT genetype frequencies of the SNP (rs352140 ) were 20.8%, 61.0% and 18.2% respectively. rs5743836 is non-polymorphic in our population, all were TT genetype. Single loci analysis suggested that the T allele at position of rs352140 was significantly associated with the susceptibility to SLE (Z=2.357, P=0.018402) in dominant model, but not in additive or recessive model. Genetype analysis showed that individuals with CT genetype had greater susceptibility to SLE than those without (Z=2.004, P= 0.045067). The univariate conditional logistic regression model (α=0.20) showed that some enviromental factors were significant between the SLE cases and their normal siblings, such as sex[P=0.001, OR=0.139(0.043-0.450)], noise[P=0.026, OR=3.541(1.160-10.808)], hypersensitiveness [P=0.000, OR=6.538(2.684-15.927)]; Multi-conditional logistic regression model showed that a possible interaction of hypersensitiveness*rs352140 [P=0.063,OR=1.887(0.966-3.686)], it showed that the rs352140 of TLR9 gene may not be the independent risk factor.Conclusions Our study suggests that a single nucleotide polymorphism (rs352140) in the exon 2 region of TLR9 gene may be a susceptibility factor for SLE in Anhui Han population, and the promoter region of TLR9 gene polymorphism(rs5743836) is non-polymorphic in Anhui Han population; Many environmental risk factors are related to systemic lupus erythematosus, and rs352140 gene polymorphism increase the risk of persons with hypersensitiveness to development of systemic lupus erythematosus.