Association Study Of Interleukin-10R1, R2Gene Single Nucleotide Polymorphisms With Systemic Lupus Erythematosus

Background Interleukin-10(IL-10) is a pleiotropic cytokine, plays an important rolein the pathogenesis of systemic lupus erythematosus (SLE). IL-10signals are mediatedthrough the IL-10receptor (IL-10R), consisting of IL-10receptor1(IL-10R1) andIL-10receptor2(IL-10R2). Unlike IL-10protein, few studies have focused on thepotential association between IL-10R and SLE.Objective To investigate the association of IL-10R1gene single nucleotidepolymorphism (SNP) rs9610(A/G) and IL-10R2gene rs2834167(A/G) with SLE andits clinical features.Methods According to the American College of Rheumatology (ACR)1997RevisedCriteria for the classification of SLE. A total of667SLE patients from Anhui ProvincialHospital and the First Affiliated Hospital of Anhui Medical University were recruited inthis study.676healthy controls were enrolled. The general information and clinical dataof subjects were collected by using self-designed questionnaire. Genotypes of IL-10R1gene rs9610(A/G) and IL-10R2gene rs2834167(A/G) were detected by TaqMan SNPallelic discrimination using ABI7300polymerase chain reaction (PCR). Frequencies ofallele and genotype were compared between patients and controls. Meanwhile, allellicand genotypic distribution were also analyzed between SLE patients with differentclinical phenotypes. Results (1) For IL-10R1gene rs9610, allelic frequencies for A and G were61.99%,38.01%in SLE patients and63.46%,36.54%in controls. There was no significantdifference between patients and controls (2=0.62, P=0.432). Genotypic frequencies forAA, AG and GG were38.08%,47.83%,14.09%in SLE patients and42.16%,42.60%,15.24%in controls. Multivariate Logistic regression analysis adjusted for age failed toshow a positive association between any of the genotypes and susceptibility to SLE(P>0.05). Similarly, we also failed to find any significant association between thispolymorphism and SLE risk either at dominant or recessive model.For IL-10R2gene rs2834167(A/G), allelic frequencies for A and G were44.53%,55.47%in SLE patients and40.16%,59.84%in controls with a statistical significance(2=5.24, P=0.022). Allele A was associated with a1.196-fold (95%CI:1.026-1.394)greater risk for the occurrence of SLE compared with G allele. Genotypic frequenciesfor AA, AG and GG were19.19%,50.67%,30.13%in SLE patients and17.01%,46.30%,36.69%in controls. After adjusting for age, it indicated that genotype AGmight confer susceptibility to SLE compared with the GG genotype (OR=1.334,95%CI:1.047-1.699). We also found a statistical significance in the dominant model (AA+AGvs GG,2=6.46, P=0.011, OR=1.343,95%CI:1.070-1.687). However, in the recessivemodel, the positive association was not observed (P>0.05).(2) It showed that IL-10R2gene rs2834167(A/G) possibly associated with the clinicalfetures malar rash and oral ulcer in SLE patients. We found IL-10R2gene rs2834167Aallele might play a protective role for malar rash in patients using dominant model(AA+AG vs GG, OR=0.674,95%CI:0.480-0.949), while in the recessive model, itindicated that A allele may increase the risk of oral ulcer in SLE patients (AA vsGG+AG, OR=1.827,95%CI:1.042-3.203). Conclusions IL-10R1gene rs9610(A/G) may not be associated with the developmentof SLE or its general clinical features. Interestingly, IL-10R2gene rs2834167(A/G)might confer susceptibility to SLE. Additionally, it also associated with the clinicalfetures malar rash and oral ulcer in SLE patients.