ABSTRACT
OBJECTIVE: The interleukin 2 (IL-2) and interleukin 21 (IL-21) locus at chromosome 4q27 has been associated with several autoimmune diseases, and both genes are related to immune system functions. The aim of this study was to evaluate the role of the IL-2/IL-21 locus in systemic sclerosis (SSc). PATIENTS AND METHODS: The case control study included 4493 SSc Caucasian patients and 5856 healthy controls from eight Caucasian populations (Spain, Germany, The Netherlands, USA, Italy, Sweden, UK and Norway). Four single nucleotide polymorphisms (rs2069762, rs6822844, rs6835457 and rs907715) were genotyped using TaqMan allelic discrimination assays. RESULTS: We observed evidence of association of the rs6822844 and rs907715 variants with global SSc (pc=6.6E-4 and pc=7.2E-3, respectively). Similar statistically significant associations were observed for the limited cutaneous form of the disease. The conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs6822844 polymorphism. Consistently, the rs2069762A-rs6822844T-rs6835457G-rs907715T allelic combination showed evidence of association with SSc and limited cutaneous SSc subtype (pc=1.7E-03 and pc=8E-4, respectively). CONCLUSIONS: These results suggested that the IL-2/IL-21 locus influences the genetic susceptibility to SSc. Moreover, this study provided further support for the IL-2/IL-21 locus as a common genetic factor in autoimmune diseases.
Subject(s)
Interleukin-2/genetics , Interleukins/genetics , Scleroderma, Systemic/genetics , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Logistic Models , Male , Polymorphism, Single Nucleotide , Scleroderma, Diffuse/ethnology , Scleroderma, Diffuse/genetics , Scleroderma, Limited/ethnology , Scleroderma, Limited/genetics , Scleroderma, Systemic/ethnology , White People/geneticsABSTRACT
OBJECTIVE: To assess the prevalence of systemic sclerosis (SSc) in a French multi-ethnic population and to examine ethnic differences. METHODS: This survey was conducted in Seine-Saint-Denis County, a suburb of Paris, home to 1,094,412 adults (>/=15 yr), among whom 26% are of non-European background with mainly northern and sub-Saharan African, Asian and Caribbean ancestries. The study period comprised the entire calendar year 2001. Patients were ascertained through four sources: public and private hospitals, general practitioners and community specialists, the French SSc patient support group, and the National Public Health Insurance System database. Only cases meeting either the 1980 ACR and/or LeRoy and Medsger's classification criteria were included and assigned to three clinical subsets: limited (normal skin) (l), limited cutaneous (lc) or diffuse cutaneous (dc) SSc. Capture-recapture (CR) analyses using log-linear modelling were performed to correct for incomplete case finding. RESULTS: We retained a total of 119 patients with SSc, including 15 extrapolated from inaccessible files. CR analysis estimated that 54.2 additional cases were missed by all the sources. The overall SSc prevalence (per million adults) was 158.3 (95% confidence interval, 129-187); those of lSSc, lcSSc and dcSSc were, respectively, 32.3 (16-48), 83.1 (66-101) and 42.9 (25-60); and respective values for Europeans and non-Europeans were 140.2 (112-170) and 210.8 (128-293). CONCLUSION: Regarding the heterogeneity of previously published estimates, this population-based survey using CR analysis might contribute to obtaining a better appraisal of SSc prevalence. Despite overlapping confidence intervals, the higher prevalence observed for non-Europeans could support potential influences of ethnic origin on the pathogenesis of SSc.
