Association of angiotensin I-converting enzyme gene insertion/deletion polymorphism with rheumatic heart disease in Indian population and meta-analysis

Abstract

Rheumatic heart disease (RHD) is one of the most severe consequences of rheumatic fever. It has been suggested that angiotensin I-converting enzyme (ACE) may be involved in the increased valvular fibrosis and calcification in the pathogenesis of RHD. We conducted a case-control study to look for association of ACE I/D polymorphism with RHD in Indian population. The study incorporated 300 patients (170 males and 130 females) with RHD, and 200 controls (118 males and 82 females). We also subgrouped RHD patients into mitral valve lesion (MVL) and combined valve lesion (CVL). ACE I/D polymorphism was identified using polymerase chain reaction method. We also performed a meta-analysis of three published studies and the present study (636 RHD cases and 533 controls) to evaluate the association between the ACE I/D polymorphisms and RHD risk. A significant difference in ACE ID and DD genotypes distribution between RHD cases (OR = 1.62, 95% CI = 1.11-2.36 and OR = 2.08, 95% CI = 1.02-4.15, respectively) and corresponding controls was observed. On comparing the ACE genotypes of MVL and CVL subgroups with controls, ID and DD genotypes were also significantly associated with CVL (FDR Pcorr = 0.009, OR = 2.19 and FDR Pcorr = 0.014, OR = 3.29, respectively). Meta-analysis also suggested association of the ACE D allele (FDR Pcorr = 0.036, OR-1.22, 95% CI 1.02-1.45) with RHD. In conclusion, ACE ID and DD genotypes are associated with an increased risk of RHD, particularly CVL. This suggests that the ACE I/D gene polymorphism may play an important role in the pathogenesis of RHD.

Genetic variants in rheumatic fever and rheumatic heart disease

“…The meta‐analysis, which included the highest number of articles (nine), and a superior number of study participants (1,333 RHD cases and 1,212 controls), showed no association between ACE I/D and the risk of RHD (Tian et al, ). These results were in contrast with two previous meta‐analyses conducted in RHD cases: a meta‐analysis by Shang et al (), including six studies consisting a total of 981 RHD cases and 901 controls suggested that the ACE I/D SNP was significantly associated with RHD and a meta‐analysis conducted by Gupta et al, , which included four articles constituting 636 RHD cases and 533 controls reported a significant association between the ACE I/D and RHD. To date, no genetic variant in the ACE gene has been investigated in RF cases.…”

Angiotensin-converting enzyme gene insertion/deletion polymorphism in Saudi patients with rheumatic heart disease

“… 8 The ACE I/D polymorphism has been associated with an increased risk of RHD in different populations. 9 - 11 With respect to Arab populations, only one study from Egypt has reported that the ACE DD genotype is associated with an increased risk of RHD. 12 Since there is a lack of data regarding the role of this polymorphism in the Saudi population, we evaluated the ACE I/D polymorphism in Saudi patients with RHD.…”

The Human Leukocyte Antigen Locus and Susceptibility to Rheumatic Heart Disease in South Asians and Europeans

“…For the South Asian analysis, genetic material was obtained with informed consent from cases and controls recruited to two distinct studies. Specifically, we expanded an existing collection in Northern India [12][13][14][15][16], and we used samples from our existing collection of Pacific Islanders [8], specifically the Fijians of Indian descent. Cases of RHD were defined on the basis of: a history of valve surgery for RHD, a definite RHD diagnosis by echocardiography, or borderline RHD diagnosis by echocardiography with prior acute rheumatic fever [17].…”

“…In India, adults with incident or prevalent RHD were recruited as cases from a single large referral hospital, the Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh; recruitment was limited to patients with an echocardiographic diagnosis of RHD [17]. Controls were recruited based on normal echocardiograms and the absence of prior family history of rheumatic fever [12][13][14][15][16]. In total, DNA samples were obtained from 543 cases and 397 controls.…”