Dataset Information

Genetic Case-Control Study for Eight Polymorphisms Associated with Rheumatoid Arthritis.

ABSTRACT: Rheumatoid arthritis (RA) is an autoimmune disease which has a significant socio-economic impact. The aim of the current study was to investigate eight candidate RA susceptibility loci to identify the associated variants in Egyptian population. Eight single nucleotide polymorphisms (SNPs) (MTHFR-C677T and A1298C, TGF?1 T869C, TNFB A252G, and VDR-ApaI, BsmI, FokI, and TaqI) were tested by genotyping patients with RA (n = 105) and unrelated controls (n = 80). Associations were tested using multiplicative, dominant, recessive, and co-dominant models. Also, the linkage disequilibrium (LD) between the VDR SNPs was measured to detect any indirect association. By comparing RA patients with controls (TNFB, BsmI, and TaqI), SNPs were associated with RA using all models. MTHFR C677T was associated with RA using all models except the recessive model. TGF?1 and MTHFR A1298C were associated with RA using the dominant and the co-dominant models. The recessive model represented the association for ApaI variant. There were no significant differences for FokI and the presence of RA disease by the used models examination. For LD results, There was a high D' value between BsmI and FokI (D' = 0.91), but the r(2) value between them was poor. All the studied SNPs may contribute to the susceptibility of RA disease in Egyptian population except for FokI SNP.

SUBMITTER: Saad MN

PROVIDER: S-EPMC4492599 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Genetic Case-Control Study for Eight Polymorphisms Associated with Rheumatoid Arthritis.

Saad Mohamed N MN Mabrouk Mai S MS Eldeib Ayman M AM Shaker Olfat G OG

PloS one 20150706 7

Rheumatoid arthritis (RA) is an autoimmune disease which has a significant socio-economic impact. The aim of the current study was to investigate eight candidate RA susceptibility loci to identify the associated variants in Egyptian population. Eight single nucleotide polymorphisms (SNPs) (MTHFR-C677T and A1298C, TGFβ1 T869C, TNFB A252G, and VDR-ApaI, BsmI, FokI, and TaqI) were tested by genotyping patients with RA (n = 105) and unrelated controls (n = 80). Associations were tested using multipl ...[more]

PMID: 26147289

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Project description: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) × 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.

Dataset Information

Genetic Case-Control Study for Eight Polymorphisms Associated with Rheumatoid Arthritis.

Publications

Genetic Case-Control Study for Eight Polymorphisms Associated with Rheumatoid Arthritis.

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