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TGF-β1 +869C/T polymorphism increases susceptibility to rheumatoid arthritis in North Indian population

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Abstract

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.

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Acknowledgments

The manuscript has not been previously published nor has it been submitted simultaneously for publication elsewhere. The Indian Council of Medical Research (ICMR), New Delhi (India), is highly acknowledged for the Grant support to academic research work.

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  1. Rheumatology Laboratory, Department of Biotechnology, Chhatrapati Shahu Ji Maharaj University, Kanpur, India

    Sipahee Lal Patel & Varsha Gupta

  2. Community Health Center, Shivrajpur, Kanpur, India

    Jaya Prakash

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Patel, S.L., Prakash, J. & Gupta, V. TGF-β1 +869C/T polymorphism increases susceptibility to rheumatoid arthritis in North Indian population. Clin Rheumatol 39, 2881–2888 (2020). https://doi.org/10.1007/s10067-020-05064-w

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