Association of BLK and BANK1 Polymorphisms and Interactions With Rheumatoid Arthritis in a Latin-American Population

Abstract

Introduction: BLK has been identified as a risk factor to rheumatoid arthritis (RA) primarily in Asian or European-derived populations. However, this finding has not been evaluated in other populations such as Latin-Americans, except for Colombians. On the other hand, BANK1 single nucleotide variants (SNVs) have been scarcely studied in RA patients. Objective: The aim of this study was to determine whether the BLK rs2736340T/C, rs13277113A/G, and BANK1 rs10516487G/A (R61H) and rs3733197G/A (A383T) polymorphisms are risk factors to RA in a sample of patients from Central Mexico. Materials and Methods: We studied 957 women; 487 controls and 470 patients with RA by means of a TaqMan® SNP genotyping assay with fluorescent probes for the BLK rs13277113A/G, rs2736340T/C and BANK1 10516487G/A (R61H) and rs3733197G/A (A383T) variants. Result: The BLK rs2736340T/C and rs13277113A/G variants were associated with risk for RA: C vs T; OR 1.39, p = 0.001, and G vs A; OR 1.37, p = 0.004, respectively. In addition, there was also an association between BANK1 R61H and RA: A vs G; OR 1.49, p = 0.003, but no with BANK1 A383T. We also identified an interaction significant between genotypes of BLK rs2736340T/C-BANK1 rs10516487G/A and RA: OR 1.65, p = 0.0001. Conclusions: Our data suggest that both BLK and BANK1 confer susceptibility to RA in Mexican patients. The individual association of BANK1 rs1054857G/A with RA had not been previously reported in a particular population (except for pooled patients from several countries), therefore, our study presents the first evidence of association between this BANK1 variant and RA.

CASP1 Gene Polymorphisms and BAT1-NFKBIL-LTA-CASP1 Gene–Gene Interactions Are Associated with Restenosis after Coronary Stenting

“…In the last decade, several studies have shown that the analysis of gene–gene interactions between different genes plays an important role in the risk of developing complex diseases such as coronary heart disease, rheumatoid arthritis, and hyperlipidemia [ 26 , 27 , 28 , 29 ]. In this study, we evaluated whether the gene–gene interaction between BAT1 rs2239527 C / G , NFKBIL1 rs2071592 T / A , LTA rs1800683 G / A , CASP1 rs580253 A / G, and CASP1 rs501192 A / G polymorphisms could be jointly associated with the risk of developing restenosis after stenting using the multifactor dimensionality reduction (MDR) program.…”

IgA Vasculitis: Influence of CD40, BLK and BANK1 Gene Polymorphisms

“…Three polymorphisms within CD40 (rs1883832, rs1535045 and rs4813003) and BLK (rs2254546, rs2736340, rs2618476) genes as well as two genetic variants within BANK1 (rs10516487 and rs3733197) were selected in this study. These eight specific variants were selected considering that they were related to numerous inflammatory disorders [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. In addition, potential functional consequences were previously proposed for some of these polymorphisms [ 8 , 18 , 19 , 36 ].…”

“…In this regard, BLK is a src family nonreceptor tyrosine kinase [ 5 ] with a relevant role in the development and receptor signaling of B-cells [ 6 ], whereas BANK1 is an adaptor/scaffold that participates in B-cell activation and signalization [ 7 , 8 ]. Interestingly, CD40 [ 9 , 10 , 11 , 12 , 13 ], BLK [ 7 , 14 , 15 , 16 , 17 , 18 ] and BANK1 [ 7 , 8 , 18 , 19 ] genes are identified as susceptibility loci for several inflammatory diseases. Likewise, CD40 and BLK variants are known as susceptibility factors for different forms of vasculitis, specifically for the development of ischemic manifestations in patients with giant cell arteritis [ 20 , 21 ] and for Kawasaki disease [ 13 , 22 ], supporting the relevance of B-cell activation in the pathophysiology of both vasculitides.…”

BLK polymorphisms and expression level in neuromyelitis optica spectrum disorder

“… 13 , 14 Furthermore, BLK is involved in the immune tolerance of B lymphocytes, affecting the function of B cells, which may lead to autoreactive or regulatory cellular responses, increasing the risk of autoimmune diseases. Most studies have provided reliable evidence that the single nucleotide polymorphisms (SNPs) of BLK exert a key role in susceptibility to various autoimmune disorders, such as SLE, 15 rheumatoid arthritis (RA), 16 SS, 17 thyroid disorders, 18 and systemic sclerosis. 19 Similarly, NMOSD is also mainly a B cell‐mediated autoimmune disease.…”