Objective: To determine whether 7 candidate genes, including tumor necrosis factor receptor II, bcl-2, CTLA-4, interleukin-10 (IL-10), CD19, Fcy receptor type IIA (CD32), and IL-1 receptor antagonist, may contribute to susceptibility to systemic lupus erythematosus (SLE) in the Italian population.
Methods: The association with SLE of intragenic markers for each candidate gene, including either microsatellites or dimorphisms, was analyzed. Gene frequencies of these gene markers were compared for patients and ethnically matched controls. Significance was tested by chi-square test on 2 x 2 tables and by Monte Carlo simulation on 2 x N tables.
Results: A significant increase was found in SLE patients (0.170 versus 0.095; chi2y = 4.11, P = 0.0425) in the frequency of the 140-basepair allele of the IL10.G microsatellite located in the promoter region of the IL-10 gene. This finding was confirmed in a second independent panel where, again, the frequency of the 140-bp allele was found to be significantly increased in SLE patients versus controls (0.176 versus 0.086; chi2y = 3.95, P = 0.0470). Considering the 2 panels together, the relative risk conferred by the presence of the 140-bp allele was 1.78 (95% confidence interval 1.19-2.66). Conversely, no significant association was detected for the remaining 6 candidate genes, even when the patients were stratified according to the presence of different clinical and immunologic features according to the presence of the associated HLA-DR or IL-10 alleles.
Conclusion: Of the 7 candidate genes tested, only IL-10 was significantly associated with SLE in Italian patients. This genetic marker represents, apart from HLA, the only genetic susceptibility factor for SLE found so far in the Italian population.