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, 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 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. TGFβ1 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 r2 value between them was poor. All the studied SNPs may contribute to the susceptibility of RA disease in Egyptian population except for FokI SNP.

MTRR A66G, RFC1 G80A, and MTHFR C677T and A1298C Polymorphisms and Disease Activity in Mexicans with Rheumatoid Arthritis Treated with Methotrexate

“…Studies of the genotype and allele frequencies of the polymorphisms that we analyzed have revealed that they vary widely worldwide (Dávalos et al , 2001 ; Boughrara et al , 2015 ; Saad et al , 2015a ; Li et al , 2016 ; Remuzgo-Martínez et al , 2016 ). Several studies have investigated the associations of these polymorphisms with autoimmune diseases, including systemic lupus erythematosus (Summers et al , 2008 ), multiple sclerosis (Naghibalhossaini et al , 2015 ), and thyroiditis (Arakawa et al , 2012 ).…”

“…Previous studies have investigated associations between RA clinical activity and treatment response and the deoxyribonucleic acid (DNA) variants of genes associated with folic acid metabolism such as MTRR , RFC1 , and MTHFR (Berkun et al , 2004 ; Hughes et al , 2006 ; Wessels et al , 2006 ; Rubini et al , 2008 ; Inanir et al , 2013 ; Salazar et al , 2014 ; Saad et al , 2015a , 2015b , 2016 ; Muralidharan et al , 2016 ; Remuzgo-Martínez et al , 2016 ). MTRR gene is located on chromosome 5p15.3 and encodes for the enzyme methionine synthase reductase, involved in the reductive regeneration of cob(I)alamin (vitamin B12) cofactor required for the maintenance of methionine synthase in a functional state (Jacques, 2003 ).…”

Association of the MTHFR 677C>T and 1298A>C polymorphisms and male infertility risk: a meta-analysis

“…Homozygotes do not show high serum homocysteine levels for the A1298C allele. But individuals with combined heterozygote A1298C and C677T polymorphisms have biochemical characteristics similar to C677T homozygotes with elevated levels of homocysteine and decreased levels of folate [15,16]. Numerous studies have examined the association between MTHFR polymorphism and male infertility, but the conclusions are argumentative [17].…”

Studying the effects of haplotype partitioning methods on the RA-associated genomic results from the North American Rheumatoid Arthritis Consortium (NARAC) dataset

“…These SNPs are in or near genes that commonly play a role in immunity. Most of these genes are linked to RA pathogenesis [1], [2], [3], [4].…”