Association Study Of Polymorphisms In Interleukin-21with Systemic Lupus Erythematosus

Objective To investigate the association of interleukin-21(IL-21) gene single nucleotidepolymorphism (SNP) with systemic lupus erythematosus (SLE), so as to provide newevidence for exploring the genetic factors of SLE.Methods A total of605independent SLE patients from Anhui Provincial Hospital andthe First Affiliated Hospital of Anhui Medical University and666healthy controls wererecruited. Diagnosis of SLE and classification of the patients into clinical subsets werecarried out according to the American College of Rheumatology (ACR) criteria for SLE(1997). Controls were unrelated healthy individuals without history of autoimmunediseases. The general information and clinical data of subjects were collected usingself-designed questionnaire. The genotypes of intronic SNP (rs2221903, rs907715) weregenotyped in all patients and controls by TaqMan SNP allelic discrimination on an ABI7300PCR Instrument. Allele, genotype and haplotype frequencies were comparedbetween patients and controls. In addition, allele and genotype frequencies werecompared between different clinical phenotypes in SLE patients.Results (1) For SNP rs2221903, allele frequencies for C and T were10.6%,89.4%inSLE patients and13.2%,86.8%in controls. The odds for carrying the risk allele T were1.287greater in SLE patients compared to controls (95%CI,1.010-1.640). Genotypefrequencies for CC, CT and TT were1.0%,19.2%,79.8%in SLE patients and0.8%,24.9%,74.3%in controls. Multivariate logistic regression analysis adjusted for sex andage failed to show an association between any of the genotypes and susceptibility toSLE (P>0.05). However, The odds for carrying TT homozygous genotype were1.368 greater (95%CI,1.050-1.781).For SNP rs907715, allele frequencies for T and C were44.7%,55.3%both in SLEpatients and controls, there was no significant difference (χ~2=0.00, P=0.983). Genotypefrequencies for TT, CT and CC were20.5%,48.4%,31.1%in SLE patients and19.2%,50.9%,29.9%in controls. Multivariate logistic regression analysis adjusted for sex andage failed to show an association between any of the genotypes and susceptibility toSLE (P>0.05).(2) In SLE patients, no significant associations were observed between SNP rs2221903and rs907715with the lupus nephritis (LN), malar rash, discoid rash, photosensitivity,and arthritis (P>0.05). About oral ulcers, the odds for carrying allele C of SNP rs907715were1.804(95%CI,1.191-2.734), and the odds for carrying CC homozygous genotypewere2.493(95%CI,1.492-4.351).(3) The haplotype construction result showed that haplotype frequencies for CC, CT, TCand TT were0.098,0.008,0.455,0.493in SLE patients and0.129,0.003,0.424,0.444in control subjects, respectively. There was significant difference between CC haplotypefrequencies in SLE patients and in controls (χ~2=5.98, P=0.015).Conclusions IL-21gene intronic rs2221903may be associated with SLE geneticsusceptibility and rs907715may be associated with oral ulcers susceptibility in SLEpatients. The CC haplotype constructed by two SNP may be associated with SLE.