Lack of replication of interactions between polymorphisms in rheumatoid arthritis susceptibility: case-control study
Por:
Ferreiro-Iglesias, A, Calaza, M, Perez-Pampin, E, Longo, FJL, Marenco, JL, Blanco, FJ, Narvaez, J, Navarro, F, Canete, JD, de la Serna, AR, Gonzalez-Alvaro, I, Herrero-Beaumont, G, Pablos, JL, Balsa, A, Fernandez-Gutierrez, B, Caliz, R, Gomez-Reino, JJ, Gonzalez, A
Publicada:
1 ene 2014
Resumen:
Introduction: Approximately 100 loci have been definitively associated with rheumatoid arthritis (RA) susceptibility. However, they explain only a fraction of RA heritability. Interactions between polymorphisms could explain part of the remaining heritability. Multiple interactions have been reported, but only the shared epitope (SE) x protein tyrosine phosphatase nonreceptor type 22 (PTPN22) interaction has been replicated convincingly. Two recent studies deserve attention because of their quality, including their replication in a second sample collection. In one of them, researchers identified interactions between PTPN22 and seven single-nucleotide polymorphisms (SNPs). The other showed interactions between the SE and the null genotype of glutathione S-transferase Mu 1 (GSTM1) in the anti-cyclic citrullinated peptide-positive (anti-CCP+) patients. In the present study, we aimed to replicate association with RA susceptibility of interactions described in these two high-quality studies.
Methods: A total of 1,744 patients with RA and 1,650 healthy controls of Spanish ancestry were studied. Polymorphisms were genotyped by single-base extension. SE genotypes of 736 patients were available from previous studies. Interaction analysis was done using multiple methods, including those originally reported and the most powerful methods described.
Results: Genotypes of one of the SNPs (rs4695888) failed quality control tests. The call rate for the other eight polymorphisms was 99.9%. The frequencies of the polymorphisms were similar in RA patients and controls, except for PTPN22 SNP. None of the interactions between PTPN22 SNPs and the six SNPs that met quality control tests was replicated as a significant interaction term-the originally reported finding-or with any of the other methods. Nor was the interaction between GSTM1 and the SE replicated as a departure from additivity in anti-CCP+ patients or with any of the other methods.
Conclusions: None of the interactions tested were replicated in spite of sufficient power and assessment with different assays. These negative results indicate that whether interactions are significant contributors to RA susceptibility remains unknown and that strict standards need to be applied to claim that an interaction exists.
Filiaciones:
Ferreiro-Iglesias, A:
Hosp Clin Univ Santiago, Inst Invest Sanitaria, Lab Invest 10, Santiago De Compostela 15706, Spain
Hosp Clin Univ Santiago, Inst Invest Sanitaria, Rheumatol Unit, Santiago De Compostela 15706, Spain
Calaza, M:
Hosp Clin Univ Santiago, Inst Invest Sanitaria, Lab Invest 10, Santiago De Compostela 15706, Spain
Hosp Clin Univ Santiago, Inst Invest Sanitaria, Rheumatol Unit, Santiago De Compostela 15706, Spain
Perez-Pampin, E:
Hosp Clin Univ Santiago, Inst Invest Sanitaria, Lab Invest 10, Santiago De Compostela 15706, Spain
Hosp Clin Univ Santiago, Inst Invest Sanitaria, Rheumatol Unit, Santiago De Compostela 15706, Spain
Longo, FJL:
Hosp Univ Gregorio Maranon, Rheumatol Unit, Madrid 28009, Spain
Marenco, JL:
Hosp Univ Valme, Rheumatol Unit, Seville 41014, Spain
Blanco, FJ:
INIBIC CH Univ A Coruna, Rheumatol Unit, La Coruna 15006, Spain
Narvaez, J:
Hosp Univ Bellvitge, Dept Rheumatol, Barcelona 08907, Spain
Navarro, F:
Hosp Univ Virgen Macarena, Rheumatol Unit, Seville 41009, Spain
Canete, JD:
Hosp Clin Barcelona, Dept Rheumatol, E-08036 Barcelona, Spain
IDIBAPS, E-08036 Barcelona, Spain
de la Serna, AR:
Hosp Santa Creu & Sant Pau, Rheumatol Unit, Barcelona 08025, Spain
Gonzalez-Alvaro, I:
Hosp Univ La Princesa, Inst Invest Sanitaria Hosp La Princesa, Rheumatol Serv, Madrid 28006, Spain
Herrero-Beaumont, G:
Fdn Jimenez Diaz, Rheumatol Unit, E-28040 Madrid, Spain
Pablos, JL:
Inst Invest Hosp 12 Octubre, Serv Reumatol, Madrid 28041, Spain
Balsa, A:
Hosp La Paz, Rheumatol Unit, Madrid 28046, Spain
Fernandez-Gutierrez, B:
Hosp Clin San Carlos, Rheumatol Unit, Madrid 28040, Spain
Caliz, R:
Hosp Virgen de las Nieves, Granada 18014, Spain
Gomez-Reino, JJ:
Hosp Clin Univ Santiago, Inst Invest Sanitaria, Lab Invest 10, Santiago De Compostela 15706, Spain
Hosp Clin Univ Santiago, Inst Invest Sanitaria, Rheumatol Unit, Santiago De Compostela 15706, Spain
Univ Santiago de Compostela, Dept Med, Santiago De Compostela 15706, Spain
Gonzalez, A:
Hosp Clin Univ Santiago, Inst Invest Sanitaria, Lab Invest 10, Santiago De Compostela 15706, Spain
Hosp Clin Univ Santiago, Inst Invest Sanitaria, Rheumatol Unit, Santiago De Compostela 15706, Spain
Gold, Green Published
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