Association Study Of TLR4and TLR7Polymorphisms With Systemic Lupus Erythematosus

Background Systemic lupus erythematosus (SLE) is a chronic systemic autoimmunedisorder affecting multiple organ systems, which is characterized by the production ofautoantibody and ICs (immune complexes), and predominantly affects women ofchildbearing age, with a female-to-male ratio of approximately10:1. The exactpathogenesis of SLE is still unclear; it suggested that SLE is a complex disease whicharises from genetic factors and environmental factors, and genetic factors areincreasingly recognized as major contributors to SLE risk. The possible susceptibilitygenes include TLR4(Toll-like receptor4) and TLR7. In recent years, with thecompleted construction of HapMap (Human Haplotype Map) and SNPs(single-nucleotide polymorphism) haplotype map, lower-cost, hiahly efficient andhigh-throughput genotyping technologies have appeared. Association analysis hasbecome the most effective method to explore complex disease.Objective To explore whether TLR4and TLR7polymorphisms are associated with SLEsusceptibility and clinical features of SLE, a case-control study was performed on TLR4gene (rs10759932and rs11536889) and TLR7gene (rs1634323) in a Chinesepopulation with413SLE patients and426healthy controls. Genotyping was determinedusing the TaqMan genotyping assay on7300real-time reverse transcription polymerasechain reaction System.Methods Through the collecting network of SLE patients,(including the rheumatologydepartment of the Anhui Provincial Hospital and the first affiliated hospital of AnhuiMedical University), demographic, personal data and clinical data were collected byquestionnaire and reviewed by experienced physicians. A total of413SLE patients (386 female and27male), and426controls (268female and158male) were enrolled in thepresent study. The blood samples were collected from all participants. The informationdatabase was set up using EpiData3.0and Excel2003. All data were analyzed usingSPSS10.01software (SPSS Inc.,2000). Differences of genotypic and allelicfrequencies distributions in both SLE patients and healthy controls were analyzed by theChi-square test or Fisher’s exact test. Odds ratio (OR) with95%confidence interval (CI)was calculated using unconditional logistic regression with the adjustment of age andsex. Haplotype analysis was assessed using SHEsis software.Results The genotype frequencies for rs11536889G/G、C/G and C/C were64.0%,30.2%and5.8%in SLE patients with LN (lupus nephritis) and56.6%,39.4%, and4.0%in cases without LN, respectively. Multivariate logistic regression analysis adjusted forage and sex faied to show an association between any of the genotypes andsusceptibility to SLE LN (CG vs. GG: P=0.075, OR=0.668,95%CI=0.429-1.042;CC vs. GG: P=0.637, OR=1.259,95%CI=0.484-3.277; CG+CC vs. GG: P=0.132,OR=0.723,95%CI=0.474-1.103). The frequencies of G allele and C allele were79.1%、20.9%and71.9%and28.1%in the two groups, significant association wasdetected (C vs. G: P=0.022, OR=0.676,95%CI=0.483-0.946). That is to say, themutation C allele played a protective role in the pathogenesis of SLE. No significantdifferences were exhibited in the genotypic and allelic distributions for rs10759932andrs1634323in SLE susceptibility and typical clinical feature susceptibility.Conclusion No significant differences existed between the patients with SLE and thecontrols as well as SLE patients with typical clinical feature and those without for TLR4rs10759932and TLR7rs1634323. TLR4rs1634323was associated with LN in SLEpatients.