The insertion and deletion (I28005D) polymorphism of the angiotensin I converting enzyme gene is a risk factor for osteoarthritis in an Asian Indian population

Abstract

Introduction: Angiotensin I converting enzyme (ACE) insertion and deletion (I/D) polymorphism has been implicated in the pathogenesis of osteoarthritis (OA). In recent years, numerous genetic factors have been identified and implicated in OA. In this Asian Indian population-based study, we aimed to evaluate the relationship between ACE (I28005D) gene polymorphism and primary OA. We performed a case-control association study to identify and explore the correlation between clinically, radiologically diagnosed individuals with primary knee OA and the ACE I/D polymorphism. Methods: Genomic DNA was isolated from 200 samples, including 100 OA cases and 100 healthy volunteers. DNA was amplified by polymerase chain reaction (PCR) using I and D allele-specific primers. PCR products were assessed via UV visualization of products electrophoresed on 2% agarose gels. Results: The groups differed significantly in genotype distributions (p < 0.05). The primary knee OA group showed a considerably higher incidence of the DD genotype and the D allele compared to the control group (OR = 2.14, 95% CI: 1.10–4.15, p = 0.02 and OR = 2.08, 95% CI: 1.39–3.10, p = 0.0003). Conclusion: The ACE gene polymorphism I28005D was found to be associated with primary knee OA in Asian Indian populations. This is the first study in India to report that the ACE gene polymorphism is a risk factor for early onset primary knee OA.

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Susceptibility to Osteoarthritis of the Knee: A Case-Control Study and Meta-Analysis

“…In reports by Bayram et al (2011) and Inanir et al (2013), the DD genotype of the ACE gene I/D polymorphism was associated with knee OA in a Turkish study population [ 38 , 39 ]. Poornima et al (2015) observed the same phenomenon in an Asian Indian population [ 40 ]. In contrast with our hypothesis, the above three studies considered that D allele carriers had the greater risk of OA.…”

“…Of the remaining six papers, one paper did not have sufficiently detailed data for the analysis. Accordingly, five studies were included in our meta-analysis [ 36 – 40 ], and detailed data are presented in Table 3 . Our meta-analysis therefore comprised three Asian studies and three Arab studies, including our case–control study.…”

“…However, the Asian subgroup also exhibited high heterogeneity in the meta-analysis. This heterogeneity might have been due to a study of an Indian population [ 40 ]. The 1,000-Genome Project considered South Asians and East Asians to comprise different racial categories [ 42 ].…”

“…Moreover, no meta-analyses have been carried out on this subject. Only a limited number of studies have investigated the link between OA and the ACE I/D polymorphism [ 36 – 40 ]. In reports by Bayram et al (2011) and Inanir et al (2013), the DD genotype of the ACE gene I/D polymorphism was associated with knee OA in a Turkish study population [ 38 , 39 ].…”

“…However, although Hong et al (2003) and Shehab et al (2008) found a negative association between ACE alleles and knee OA, carriers of the I allele had the greater risk of OA [ 36 , 37 ]. Given these inconclusive findings in the literature, we attributed the high heterogeneity to small sample sizes (sample sizes of those studies ranged from 200 to 421 [ 36 – 40 ]). To resolve this dispute with regard to consistent evidence, we proposed a case–control study with a sample size of >800 subjects.…”