Gender-Specific Effects of Genetic Variants within Th1 and Th17 Cell-Mediated Immune Response Genes on the Risk of Developing Rheumatoid Arthritis

Autor: Miguel Ferrer, Eduardo Collantes, Teresa Vallejo, Alejandro Escudero, Rafael Cáliz, Helena Canhão, Manuela Expósito-Ruiz, Lurdes Romani, Asta Försti, Kari Hemminki, João Eurico Fonseca, Alfonso González-Utrilla, Antonio García, Eva Perez-Pampin, Carmen Belén Lupiañez, María José Soto-Pino, I. Filipescu, Juan Sainz, L. M. Canet, Juana Segura-Catena
Přispěvatelé: [Cáliz,R, Soto-Pino,MJ, Ferrer,MA, García,A, Romani,L, González-Utrilla,A, Vallejo,T] Rheumatology Department, Virgen de las Nieves University Hospital, Granada, Spain. [Canet,LM, Lupiañez,CB, Segura-Catena,J, Sainz,J] Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain. [Canhão,H, Fonseca,JE] Rheumatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal. Rheumatology Department, Santa Maria Hospital–CHLN, Lisbon, Portugal. [Escudero,A, Filipescu,I, Collantes,E] Rheumatology Department, Reina Sofía Hospital, Córdoba, Spain. [Expósito-Ruiz,M] FIBAO Fundation, Virgen de las Nieves University Hospital, Granada, Spain. [Pérez-Pampin,E] Rheumtology Unit, Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain. [Hemminki,K, Försti,A, Sainz,J] Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany. [Hemminki,K, Försti,A] Center for Primary Health Care Research, Clinical Research Center, Malmö, Sweden., This study was partially supported by grants P08-CVI-4116 from Consejerı´a de Salud de la Junta de Andalucia (Sevilla, Spain) and PI08/1051 and PI12/02688 from Fondo de Investigaciones Sanitarias (Madrid, Spain).
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Male
CCR2
Multifactor Dimensionality Reduction
lcsh:Medicine
Disease
Chemicals and Drugs::Amino Acids
Peptides
and Proteins::Proteins::Lectins [Medical Subject Headings]
Gastroenterology
Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings]
Arthritis
Rheumatoid
Risk Factors
lcsh:Science
Masculino
Chemokine CCL2
Anatomy::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes
Mononuclear::Lymphocytes::T-Lymphocytes::T-Lymphocyte Subsets::T-Lymphocytes
Helper-Inducer::Th1 Cells [Medical Subject Headings]
Células TH1
Immunity
Cellular
Sex Characteristics
Multidisciplinary
Femenino
Public Health
Global Health
Social Medicine and Epidemiology
Middle Aged
Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to Disease [Medical Subject Headings]
Humanos
Rheumatoid arthritis
Analytical
Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk [Medical Subject Headings]
Artritis Reumatoide
Female
Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings]
Sex characteristics
Research Article
medicine.medical_specialty
Receptors
CCR2
Inmunidad Celular
Check Tags::Male [Medical Subject Headings]
Predisposición Genética a la Enfermedad
Single-nucleotide polymorphism
Células Th17
Lectinas
Receptors
Cell Surface
Biology
Riesgo
Polymorphism
Single Nucleotide
Internal medicine
medicine
Humans
Genetic Predisposition to Disease
Lectins
C-Type
Allele
Gene
Demography
Anatomy::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes
Mononuclear::Lymphocytes::T-Lymphocytes::T-Lymphocyte Subsets::T-Lymphocytes
Helper-Inducer::Th17 Cells [Medical Subject Headings]
Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism
Genetic::Polymorphism
Single Nucleotide [Medical Subject Headings]
Multifactor dimensionality reduction
lcsh:R
Th1 Cells
medicine.disease
Check Tags::Female [Medical Subject Headings]
Diseases::Immune System Diseases::Autoimmune Diseases::Arthritis
Rheumatoid [Medical Subject Headings]
Immunology
Th17 Cells
lcsh:Q
Polimorfismo de Nucleótido Simple
Genotipo
Cell Adhesion Molecules
Zdroj: PLoS ONE
RUNA. Repositorio da Consellería de Sanidade e Sergas
Servizo Galego de Saúde (SERGAS)
PLoS ONE; 8(8), no e72732 (2013)
PLoS ONE, Vol 8, Iss 8, p e72732 (2013)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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