Objectives: Rheumatoid arthritis (RA) is a heterogeneous autoimmune disease, characterized by chronic inflammation, hyperplasia (swelling), tenderness, erosion of cartilage and bones in synovial joints. Transforming growth factor-β1 (TGF-β1) is an important regulator of inflammation, and its polymorphism is implicated in several diseases. Therefore, the study was done to determine whether TGF-β1 C/T gene polymorphism was associated with RA in North Indian population.
Methods: Eighty-seven (male/female: 29/58) healthy controls and 76 (male/female: 17/59) RA patients were recruited for association study between TGF-β1 +869C/T polymorphism. TGF-β1 +869C/T polymorphism was genotyped by allele specific amplification refractory mutation system polymerase chain reaction (ARMS-PCR) to test susceptibility to clinical presentation of RA patients in North Indian population by comparing RA genotypes with control groups.
Results: The genotypic association studies and dominant, recessive, and allelic models revealed that TGF-β1 +869C/T gene polymorphism is involved in the onset of RA. TGF-β1 +869 T (either TT or CT) allele and TT v/s CC (OR = 36.18, 95% CI = 11.98-109.31, P = 0.001); TT + CT v/s CC (OR = 0.16, 95% CI = 0.08-0.33, P = 0.001); TT v/s CC + CT (OR = 0.04, 95% CI = 0.1-0.09, P = 0.001); and T v/s C (OR = 0.12, 95% CI = 0.07-0.2, P = 0.001) show significant association with RA as compared with CC genotype or C alleles (P = 0.001). The patient carrying T alleles showed significant associations with increased ESR, uric acid, CRP, DAS28-ESR, and number of tender joints as compared to other genotypes. In the presence of RF, DAS-28-ESR was high in CT genotype. ESR, CRP, and swollen joint count were highest in TT genotype of RF negative patients.
Conclusions: TGF-β1 polymorphism is associated with disease activity of RA. Disease activity is strongly modulated in the presence of serum RF and TGF-β1 polymorphism. Key Points •TGF-β1 +869C/T polymorphism was found to be associated with RA in the patients. •The polymorphism showed significant association with all inflammatory parameters as ESR, CRP, and DAS-28 in RA subjects. •RF negative patients showed high ESR, CRP, and swollen joint count with TT genotype. •TGF-β1 polymorphism and serum RF are modulating disease activity in RA.
Keywords: ARMS-PCR; Genetic polymorphism; Rheumatoid arthritis; Susceptibility; TGF-β1 869C/T.