RT Journal Article
T1 Gender-Specific Effects of Genetic Variants within Th1 and Th17 Cell-Mediated Immune Response Genes on the Risk of Developing Rheumatoid Arthritis.
A1 Cáliz, Rafael
A1 Canet, Luz María
A1 Lupiañez, Carmen Belén
A1 Canhão, Helena
A1 Escudero, Alejandro
A1 Filipescu, Ileana
A1 Segura-Catena, Juana
A1 Soto-Pino, María José
A1 Expósito-Ruiz, Manuela
A1 Ferrer, Miguel Ángel
A1 García, Antonio
A1 Romani, Lurdes
A1 González-Utrilla, Alfonso
A1 Vallejo, Teresa
A1 Pérez-Pampin, Eva
A1 Hemminki, Kari
A1 Försti, Asta
A1 Collantes, Eduardo
A1 Fonseca, João Eurico
A1 Sainz, Juan
K1 Artritis Reumatoide
K1 Polimorfismo de Nucleótido Simple
K1 Células Th17
K1 Células TH1
K1 Genotipo
K1 Lectinas
K1 Riesgo
K1 Femenino
K1 Masculino
K1 Predisposición Genética a la Enfermedad
K1 Humanos
AB The present study was conducted to explore whether single nucleotide polymorphisms (SNPs) in Th1 and Th17 cell-mediated immune response genes differentially influence the risk of rheumatoid arthritis (RA) in women and men. In phase one, 27 functional/tagging polymorphisms in C-type lectins and MCP-1/CCR2 axis were genotyped in 458 RA patients and 512 controls. Carriers of Dectin-2 rs4264222T allele had an increased risk of RA (OR = 1.47, 95%CI 1.10-1.96) whereas patients harboring the DC-SIGN rs4804803G, MCP-1 rs1024611G, MCP-1 rs13900T and MCP-1 rs4586C alleles had a decreased risk of developing the disease (OR = 0.66, 95%CI 0.49-0.88; OR = 0.66, 95%CI 0.50-0.89; OR = 0.73, 95%CI 0.55-0.97 and OR = 0.68, 95%CI 0.51-0.91). Interestingly, significant gender-specific differences were observed for Dectin-2 rs4264222 and Dectin-2 rs7134303: women carrying the Dectin-2 rs4264222T and Dectin-2 rs7134303G alleles had an increased risk of RA (OR = 1.93, 95%CI 1.34-2.79 and OR = 1.90, 95%CI 1.29-2.80). Also five other SNPs showed significant associations only with one gender: women carrying the MCP-1 rs1024611G, MCP-1 rs13900T and MCP-1 rs4586C alleles had a decreased risk of RA (OR = 0.61, 95%CI 0.43-0.87; OR = 0.67, 95%CI 0.47-0.95 and OR = 0.60, 95%CI 0.42-0.86). In men, carriers of the DC-SIGN rs2287886A allele had an increased risk of RA (OR = 1.70, 95%CI 1.03-2.78), whereas carriers of the DC-SIGN rs4804803G had a decreased risk of developing the disease (OR = 0.53, 95%CI 0.32-0.89). In phase 2, we genotyped these SNPs in 754 RA patients and 519 controls, leading to consistent gender-specific associations for Dectin-2 rs4264222, MCP-1 rs1024611, MCP-1 rs13900 and DC-SIGN rs4804803 polymorphisms in the pooled sample (OR = 1.38, 95%CI 1.08-1.77; OR = 0.74, 95%CI 0.58-0.94; OR = 0.76, 95%CI 0.59-0.97 and OR = 0.56, 95%CI 0.34-0.93). SNP-SNP interaction analysis of significant SNPs also showed a significant two-locus interaction model in women that was not seen in men. This model consisted of Dectin-2 rs4264222 and Dectin-2 rs7134303 SNPs and suggested a synergistic effect between the variants. These findings suggest that Dectin-2, MCP-1 and DC-SIGN polymorphisms may, at least in part, account for gender-associated differences in susceptibility to RA.
PB Public Library of Science
YR 2013
FD 2013-08-30
LK http://hdl.handle.net/10668/1345
UL http://hdl.handle.net/10668/1345
LA en
NO Cáliz R, Canet LM, Lupiañez CB, Canhão H, Escudero A, Filipescu I, et al. Gender-Specific Effects of Genetic Variants within Th1 and Th17 Cell-Mediated Immune Response Genes on the Risk of Developing Rheumatoid Arthritis. PLoS ONE. 2013; 8(8):e72732
NO Journal Article;
DS RISalud
RD Mar 5, 2025