Insertion-deletion polymorphism of angiotensin converting enzyme and susceptibility to rheumatoid arthritis in South Gujarat population

Abstract

Rheumatoid Arthritis (RA) is a chronic inflammatory disease of synovial joints. High levels of angiotensin-converting enzyme (ACE) have been documented in RA synovial fluid (SF) and pleural effusions. The ACE gene insertion-deletion (INDEL or I/D; Intron 16; AF118569) polymorphism has been associated with the variability of serum ACE activity in which DD and II genotypes possess the highest and lowest ACE activity, respectively.The study investigated the association of ACE gene I/D polymorphism with RA in South Gujarat Population. Total 174 RA patients and 261 healthy controls were genotyped for ACE I/D polymorphism by polymerase chain reaction (PCR) method. The plasma ACE levels in 34 RA patients and 42 healthy controls were estimated by ELISA. The genotype and allele frequencies of the polymorphism were significantly differed between patients and control population (p = 0.0013; p < 0.0001 respectively), suggesting that ACE I/D polymorphism is associated with RA susceptibility in South Gujarat population. The susceptible ‘D’ allele was prevalent in RA group as compared to the control group (67.00% vs 54.00%). Though, there was no significant difference in the levels of ACE between patient and control groups (p = 0.827), the genotype-phenotype analysis revealed that individuals with DD and ID genotypes exhibit increased ACE levels as compared to the II genotypes (p = 0.0174; p = 0.0062 respectively). In addition, ‘DD’ genotype being prevalent in early age of onset group and severe RA group of patients proposes a crucial role of ACE I/D polymorphism in RA development and disease activity.Overall, our study suggests that ACE I/D polymorphism may be associated with RA susceptibility in South Gujarat Population.