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Gender-Specific Eff...
Gender-Specific Effects of Genetic Variants within Th1 and Th17 Cell-Mediated Immune Response Genes on the Risk of Developing Rheumatoid Arthritis
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Caliz, Rafael (författare)
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Maria Canet, Luz (författare)
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Belen Lupianez, Carmen (författare)
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Canhao, Helena (författare)
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Escudero, Alejandro (författare)
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Filipescu, Ileana (författare)
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Segura-Catena, Juana (författare)
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Jose Soto-Pino, Maria (författare)
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Exposito-Ruiz, Manuela (författare)
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Angel Ferrer, Miguel (författare)
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Garcia, Antonio (författare)
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Romani, Lurdes (författare)
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Gonzalez-Utrilla, Alfonso (författare)
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Vallejo, Teresa (författare)
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Perez-Pampin, Eva (författare)
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- Hemminki, Kari (författare)
- Lund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups
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- Försti, Asta (författare)
- Lund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups
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Collantes, Eduardo (författare)
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Fonseca, Joao Eurico (författare)
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Sainz, Juan (författare)
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(creator_code:org_t)
- 2013-08-30
- 2013
- Engelska.
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8
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Abstract
Ämnesord
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- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Caliz, Rafael
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Maria Canet, Luz
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Belen Lupianez, ...
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Canhao, Helena
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Escudero, Alejan ...
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Filipescu, Ilean ...
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visa fler...
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Segura-Catena, J ...
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Jose Soto-Pino, ...
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Exposito-Ruiz, M ...
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Angel Ferrer, Mi ...
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Garcia, Antonio
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Romani, Lurdes
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Gonzalez-Utrilla ...
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Vallejo, Teresa
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Perez-Pampin, Ev ...
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Hemminki, Kari
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Försti, Asta
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Collantes, Eduar ...
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Fonseca, Joao Eu ...
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Sainz, Juan
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visa färre...
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