Abstract
Objective Copy number variation (CNV) is a structural variation in the human genome that has been associated with multiple clinical phenotypes. B cells are important components of rheumatoid arthritis- (RA-) mediated immune response; hence, CNV in the regulators of B cells (such as VPREB1) can influence RA susceptibility. In this study, we aimed to explore the association of CNV in the VPREB1 gene with RA susceptibility in the Pakistani population. Methods A total of 1,106 subjects (616 RA cases, 490 healthy controls) were selected from three rheumatology centers in Pakistan. VPREB1 CNV was determined using the TaqMan® CN assay (Hs02879734_cn, Applied Biosystems, Foster City, CA, USA), and CNV was estimated by using CopyCaller® (version 2.1; Applied Biosystems, USA) software. Odds ratio (OR) was calculated by logistic regression with sex and age as covariates in R. Results A significant association between >2 VPREB1 CNV and RA risk was observed with an OR of 3.92 (95% CI: 1.27 - 12.12; p = 0.01746) in the total sample. Whereas <2 CNV showed a significantly protective effect against RA risk in women with an OR of 0.48 (95% CI: 0.29-0.79; p = 0.00381). Conclusion CNV > 2 of VPREB1 is a risk factor for RA in the total Pakistani population, while CNV < 2 is protective in women.
Highlights
Rheumatoid arthritis (RA) is a systemic autoimmune disease
In order to better understand the role of Copy number variation (CNV) in RA in this region, we have examined the association of VPREB1 CNV with RA risk in the Pakistani population
The predicted CNV was categorized into three groups: less than two (CNV < 2), equal to two (CNV = 2), or greater than two (CNV > 2)
Summary
Rheumatoid arthritis (RA) is a systemic autoimmune disease. Production of autoantibodies (anticyclic citrullinated peptide and rheumatoid factor) and inflammation of joints and synovium are the hallmarks of RA [1]. RA leads to the onerous socioeconomic burden, continuous fatigue, restricted mobility due to joint damage, disability, and, in worst cases, amputation and early death [2]. RA prevalence varies across the globe in different populations, but on average, it affects 1% of the general population and occurs more frequently in women than men [3]. The interplay of multiple genetic and environmental factors leads to the onset of RA. The genetic component accounts for 50% of the RA risk [4]
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