The role of interleukin-10 promoter polymorphisms in the clinical expression of primary Sjögren's syndrome

Abstract

Objective. To analyse the role of polymorphisms of the interleukin-10 promoter region in the epidemiologic, clinical and immunologic characteristics of patients with primary Sjögren's syndrome (SS). Methods. Sixty-three consecutive patients (59 women and four men; mean age 57 yr; range 20-83 yr) were studied in our Unit. All patients fulfilled four or more of the modified diagnostic criteria for SS proposed by the European Community Study Group in 1996. As controls, 150 healthy volunteers were recruited from the medical and laboratory staff working in our hospital. All the samples from patients and controls were analysed by PCR amplification and direct sequencing. Results. The frequency of the interleukin-10 (IL-10) GCC haplotype was higher (0.48 vs 0.34, P = 0.006) and the frequency of the IL-10 ACC haplotype lower (0.25 vs 0.39, P = 0.005) in patients with primary SS compared with healthy controls. In the genotype analysis, the frequency of the GCC/ATA genotype was higher (29 vs 11%, P = 0.001) and that of the ACC/ACC genotype lower (3 vs 12%, P = 0.044) in patients with primary SS compared with healthy controls. GCC-carriers showed an earlier onset of the disease (48.06 ± 14.98 yr vs 57.53 ± 14.20 yr, P = 0.034). The existence of systemic involvement (defined by cutaneous vasculitis, peripheral neuropathy, renal and/or pulmonary involvement) was more frequent in carriers of the GCC haplotype, although the difference did not reach statistical significance (40 vs 27%, P = 0.278). No significant differences in the haematologic (hypergammaglobulinaemia, elevated ESR) and immunologic (ANA, RF, anti-Ro/SS-A and anti-La/SS-B antibodies) parameters were observed in carriers of the GCC haplotype. Conclusion. We describe an abnormal distribution of IL-10 promoter haplotypes in patients with primary SS compared with healthy controls. This consists of a predominance of the GCC haplotype, mainly related to a higher frequency of the heterozygote haplotype GCC/ATA. The presence of the GCC haplotype does not originate a different immunologic pattern but leads to an earlier onset of primary SS.