Association of Angiotensin I-Converting Enzyme Gene Insertion/Deletion Polymorphism and IgA Nephropathy: A Meta-Analysis

Abstract

Background/Aims: The angiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been extensively examined for the association with immunoglobulin A (IgA) nephropathy (IgAN), however, conflicting results have occurred. We performed a meta-analysis to evaluate the association of ACE I/D polymorphism with IgAN in different ethnic groups. Methods: 11 studies testing the association between ACE I/D polymorphism and IgAN susceptibility, and 9 studies testing the association of ACE I/D with IgAN progression were used in this analysis. The overall odds ratio (OR) was estimated by a fixed or random effect model. Results: The overall OR for the risk of susceptibility and progression of IgAN in Asians for the DD genotype is 2.37 (95% CI 1.04–5.41) and 1.75 (95% CI 1.24–2.56). The overall OR for the D allele in Asians also showed a similar magnitude, though without statistical significance (p = 0.09, p = 0.13, respectively). In Caucasians, both the DD genotype and D allele were associated with IgAN progression (OR 1.90, 1.61, respectively), but not IgAN susceptibility (p = 0.30, p = 0.41, respectively). Conclusion: Our findings support the notion that ACE I/D polymorphism is associated with IgAN. Meanwhile, the role of ACE I/D polymorphism in Asians is different from that of Caucasians.

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism and Renoprotection in Diabetic and Nondiabetic Nephropathies

“…Indeed, comparative analyses between 1339 patients with IgA and 1881 healthy controls found that the DD compared with the II and ID genotype was associated with a more than double incidence of IgA nephropathy in Asians, but with a similar risk of disease in whites. On the contrary, comparative analyses between 2706 progressors and 1578 nonprogressors found that the ACE I/D polymorphism remarkably affected the risk of ESKD in both populations, to the extent that Asian and white carriers of the DD genotype had, respectively, a 78% and 90% excess incidence of ESKD compared with carriers of the II or ID genotypes considered together (21).…”

“…Most studies evaluated the relationships between ACE I/D and adult polycystic kidney disease (APKD) or IgA nephropathy. These studies were recently reviewed in two comprehensive meta-analyses showing that this polymorphism is not associated with the progression of APKD (20) but may affect both the incidence and progression of IgA nephropathy, although to a different extent in different considered populations (21). Indeed, comparative analyses between 1339 patients with IgA and 1881 healthy controls found that the DD compared with the II and ID genotype was associated with a more than double incidence of IgA nephropathy in Asians, but with a similar risk of disease in whites.…”

Association ofT869, C509T, G915Cgene polymorphism of transforming growth factor-β1 with IgA nephropathy risk

“…Huang et al 19 conducted a meta-analysis, and provided evidence for genetic variation at the putative promoter region of Fc fragment of IgA conferring susceptibility to IgAN, suggesting -27C and its haplotype might be causative for the susceptibility among the Chinese Han population. Yong et al 20 performed a meta-analysis to evaluate the association of ACE I/D polymorphism with IgAN in different ethnic groups, and reported that ACE I/D polymorphism was associated with IgAN. Those results indicated that the gene polymorphism of some gene sites was associated with IgAN risk.…”

High dose Losartan and ACE gene polymorphism in IgA nephritis

“…There have been various studies (Yong et al 2006;Nonoguchi et al 2007) reporting on varying renal outcome in patients with IgAN in respect of their ACE gene profile. The D alelle is believed to affect the renoprotective effects of ACEI/ARB therapy.…”

“…There have also been recent reports (Yong et al 2006;Nonoguchi et al 2007) that ACE ID polymorphism influences the responses of patients with IgAN to ACEI/ARB therapy. In a recent report, Dillon (2004) suggested that polymorphism of the ACE gene may have so far failed to predict either susceptibility to or progression of IgA nephropathy, but the D allele could predict a favourable response to renin-angiotensin blockade.…”