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Title: Association of interleukin-10 promoter haplotypes with disease susceptibility and IL-10 levels in Mexican patients with systemic lupus erythematosus
Author: Palafox-Sanchez, C.A.
Oregon-Romero, E.
Salazar-Camarena, D.C.
Valle, Y.M.
Machado-Contreras, J.R.
Cruz, A.
Orozco-Lopez, M.
Orozco-Barocio, G.
Vazquez-Del Mercado, M.
Munoz-Valle, J.F.
Issue Date: 2014
Abstract: Systemic lupus erythematosus (SLE) is the prototype autoimmune rheumatic disease. The etiology of this disease is incompletely understood; however, environmental factors and genetic predisposition are involved. Cytokine-mediated immunity plays a crucial role in the pathogenesis of SLE. We investigate the association of interleukin-10 (IL-10) promoter polymorphisms and their haplotypes in SLE patients from the western Mexico. One hundred and twenty-five SLE patients fulfilling the 1997 ACR criteria and 260 unrelated healthy subjects (HS), both Mexican mestizos, were genotyped for IL-10 −1082A>G, −819C>T, and −592C>A polymorphisms. Haplotypes were inferred using the expectation–maximization algorithm, then allele and haplotype distributions were compared between patients and HS, as well as patients with different clinical variables. We identified at −1082, −819, and −592 four predominant haplotypes ACC (43.70 % in patients vs 46.55 % in HS), ATA (21.45 vs 22.97 %), GCC (16.28 vs 14.21 %), and GTA (14.12 vs 14.12 %). The ATC haplotype was more frequent in SLE respect to HS, suggesting a risk effect (3.23 vs 1.05 %; OR 3.55, CI 1.14–11.11; p = 0.0293). SLE patient carriers of −592 CC genotype as well as the dominant model of inheritance showed higher sIL-10 respect to AA genotype, suggesting that −592 C allele is associated with increased production of the cytokine (p < 0.05). The ACC haplotype had higher IL-10 serum levels and higher values of Mexican version of the Systemic Lupus Erythematosus Disease Activity Index compared with the other haplotype carriers; however, no association was found regarding autoantibodies. Our data suggest that the IL-10 promoter haplotypes play an important role in the risk of developing SLE and influence the production of IL-10 in Mexican population. Nevertheless, further studies are required to analyze the expression of mRNA as well as to investigate the interacting epigenetic factors that could help to define the true contribution of this marker in SLE pathogenesis. © 2014 Springer-Verlag Italia
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