Genetic Association Studies to Find Single Nucleotide Polymorphisms Role in Rheumatoid Arthritis Patients in North Indian Population

Abstract

The present case-control study was conducted during May 2019 to June 2022 to identify the association of HLA gene variants rs13192471 (HLA-DRB1), rs6457617 (HLA-DQB1) and ARL15 gene variant rs255758 in 188 Rheumatoid Arthritis cases and 310 healthy controls at SGRD University of Health Sciences, Amritsar in collaboration with SMVD University, Katra. Rheumatoid arthritis (RA) is a systemic, chronic, inflammatory, and autoimmune disease which is characterized by the progressive ruination of joint structures. The Human Leukocyte Antigens (HLA) genes: HLA-DRB1 and HLA-DQB1, presented on human chromosome 6, are involved in the immune system. Various studies involving GWAS, meta-analysis, and replication studies have shown the association of HLA-DRB1 variant rs13192471 and HLA-DQB1 variant rs6457617, and ARL15 rs255758 with RA susceptibility in different population groups. In this study, DNA was isolated from 188 RA cases and 310 healthy controls, followed by qualitative and quantitative analyses. The genotyping was performed on RT-PCR (Real time polymerase chain reaction) using TaqMan Allele Discrimination Assay and statistically analyzed. The statistical analyses of the genotyping data showed a significant association (p=0.005) of variant rs13192471 (HLA-DRB1) with RA susceptibility with C as risk allele and increased risk in dominant model (CT+CC vs TT; p=0.004), whereas the variant rs6457617 (HLA-DQB1) did not show an association (p = 0.275) with RA in the studied population cohort. The variant rs255758 of ARL15 gene was significantly associated with RA susceptibility in studied population cohort (p= 0.024) with C as risk allele and increased risk in recessive model (CC vs CA+AA; p=0.004). The present study successfully replicated the association of HLA-DRB1 variant rs13192471 and ARL15 variant rs255758 in the population group of North-west India. It is pertinent to screen these variants for RA susceptibility in other population groups of India before their use as potential genetic biomarkers in Indian population.