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Título : The -319C/+49G/CT60G Haplotype of CTLA-4 Gene Confers Susceptibility to Rheumatoid Arthritis in Mexican Population
Autor: NORMA TORRES CARRILLO
Heriberto Ontiveros Mercado
NORA MAGDALENA TORRES CARRILLO
ISELA PARRA ROJAS
HECTOR RANGEL VILLALOBOS
MARIA GUADALUPE RAMIREZ DUEÑAS
SERGIO RAMON GUTIERREZ UREÑA
Yeminia Valle
Jose Francisco Muñoz Valle
Palabras clave : BIOLOGÍA Y QUÍMICA;Ciencias de la vida;Genética;Genética humana;Enfermedades reumáticas;Artritis reumatoide;Rehumatic diseases;Rheumatoid arthritis;México;Mexico
Fecha de publicación: 2013
Editorial : Springer
Descripción : Several single nucleotide polymorphisms (SNPs) within the CTLA-4 gene and elevated serum levels of soluble CTLA-4 (sCTLA-4) have been associated with autoimmunity including rheumatoid arthritis (RA). In this case–control study, we evaluated the relationship between the −319C/T (rs5742909) and CT60 G/A (rs3087243) SNPs and sCTLA-4 levels in 200 RA patients and 200 control subjects (CS) from Western Mexico. Both SNPs were genotyped with the polymerase chain reaction–restriction fragment length polymorphism technique and the sCTLA-4 levels were quantified using an enzyme-linked immunosorbent assay kit. In addition, we performed a haplotype analysis, including our previous data of the +49A/G (rs231775) SNP. The G/A genotype of the rs3087243 SNP was associated with a decreased risk of RA [odd ratio (OR) 0.61, 95 % confidence interval (CI) 0.38–0.96, p = 0.024]. This protection was also observed in the negative anti-cyclic citrullinated peptide group of RA carriers of the A allele (OR 0.48, 95 % CI 0.22–1.05, p = 0.042). On the contrary, we identified the −319C/+49G/CT60G haplotype of CTLA-4 gene as a risk factor for RA (OR 1.69, 95 % CI 1.13–2.52, p = 0.01). The sCTLA-4 levels were not associated with RA (p = 0.377), but were correlated with the functional disability of these patients (r = 0.282, p = 0.012). However, in CS the C/T genotype of the rs5742909 SNP, as well as the G/G and G/A genotypes of the rs3087243 SNP were associated with higher sCTLA-4 levels (p < 0.001). In conclusion, our results suggest that the −319C/+49G/CT60G haplotype of CTLA-4 gene is a genetic marker of susceptibility to RA in Western Mexico, whereas the rs3087243 SNP confers protection against this disease. Moreover, both SNPs showed an effect on the sCTLA-4 production in our control population. However, further studies are required to evaluate the role of sCTLA-4 in RA, as well as the molecular and functional basis of the association between both CTLA-4 gene SNPs and soluble levels of CTLA-4 in CS.
URI : http://repositorio.inger.gob.mx/jspui/handle/20.500.12100/17290
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