Relationship between polymorphisms in the TGF-β receptor gene and susceptibility towards chronic obstructive pulmonary disease in Northern Indians

Chronic Obstructive Pulmonary Disease (COPD) is a multifactorial respiratory disorder influenced by genetic, environmental, and lifestyle factors such as smoking. The Transforming Growth Factor Beta Receptor 1 (TGFBR1) plays a crucial role in regulating cell proliferation, differentiation, apoptosis, and immune modulation. Dysregulation of TGFBR1 may disrupt downstream signalling, leading to chronic inflammation, extracellular matrix accumulation in COPD. The present study aimed to evaluate the association of TGFBR1 gene variants rs7040869 (G>A), rs6478974 (A>T), rs4743325 (G>T), and rs597457 (C>A) with COPD susceptibility in a North Indian population. This study comprises 500 COPD cases and 500 controls. Genotyping of the selected single-nucleotide polymorphisms (SNPs) was performed, and statistical analyses, including logistic regression, haplotype analysis, Classification and Regression Tree (CART), and Multifactor Dimensionality Reduction (MDR), were applied to assess gene-disease associations. The rs6478974 variant showed significant protective association with COPD, persisting after Bonferroni correction. Combined genotype analysis indicated that GA+GT genotypes of rs7040869 and rs4743325 increased disease risk, while CART identified rs6478974 and rs597457 as key interaction nodes. This study is the first in a North Indian cohort to identify the protective role of rs6478974 in COPD, emphasising the significance of TGFBR1 polymorphisms in disease pathogenesis and risk prediction.