Key result
ACE D allele linked to ~21% higher IgA nephropathy risk vs I allele.
Why the study?
The connection between angiotensin-converting enzyme insertion/deletion gene polymorphisms and IgA nephropathy was conflicting.
Does ACE I/D gene polymorphism increase the risk of IgA nephropathy?
Meta-Analysis (n=6,130)
Yes
Does ACE I/D gene polymorphism increase the risk of IgA nephropathy?
Odds Ratio: 1.21 (95% CI 1.1–1.32)
p-value: p=<0.001
The ACE I/D gene polymorphism, specifically the D allele and DD genotype, is associated with increased susceptibility to and progression of IgA nephropathy, particularly in Asian populations.
Background. The connection between angiotensin-converting enzyme insertion/deletion (ACE I/D) gene polymorphisms and IgA nephropathy (IgAN) was conflicting. This pooled analysis was performed to explore this issue. Methods. All eligible investigations were identified from various electronic databases, and the pooled analysis was evaluated using Stata software. Results. 27 studies with 2538 IgAN cases and 3592 controls were included. In overall subjects, ACE D allele, DD, and II genotype were associated with IgAN susceptibility (D vs. I: OR = 1.21, 95% CI: 1.10–1.32, <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>P</a:mi> <a:mo><</a:mo> <a:mn>0.001</a:mn> </a:math> ; DD vs. ID + II: OR = 1.38, 95% CI: 1.20–1.60, <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mi>P</c:mi> <c:mo><</c:mo> <c:mn>0.001</c:mn> </c:math> ; and II vs. DD + ID: OR = 0.83, 95% CI: 0.73–0.95, <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mi>P</e:mi> <e:mo>=</e:mo> <e:mn>0.007</e:mn> </e:math> ). In Asian and Chinese patients, ACE I/D gene polymorphism was also correlated with IgAN vulnerability. Moreover, ACE D allele, DD, and II genotype were correlated with the progression of IgAN (D vs. I: OR = 1.37, 95% CI: 1.09–1.73, <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mi>P</g:mi> <g:mo>=</g:mo> <g:mn>0.008</g:mn> </g:math> ; DD vs. ID + II: OR = 1.57, 95% CI: 1.06–2.31, <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:mi>P</i:mi> <i:mo>=</i:mo> <i:mn>0.024</i:mn> </i:math> ; and II vs. DD + ID: OR = 0.69, 95% CI: 0.49–0.99, <k:math xmlns:k="http://www.w3.org/1998/Math/MathML" id="M6"> <k:mi>P</k:mi> <k:mo>=</k:mo> <k:mn>0.045</k:mn> </k:math> ). Conversely, in Caucasian subjects, there was no link between ACE I/D gene polymorphism and the risk of IgAN. Conclusion. ACE I/D gene polymorphism was correlated with the vulnerability and progression of IgAN in Asian and Chinese patients, and ACE D allele and DD homozygote genotype could be adverse factors for IgAN, while the II homozygote genotype could be an advantage factor. But, no significant association was found between ACE I/D gene polymorphism and IgAN in Caucasians.
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Chu et al. (2021) conducted a meta-analysis in IgA nephropathy (n=6,130). ACE I/D gene polymorphism (D allele) vs. ACE I allele was evaluated on IgA nephropathy susceptibility (OR 1.21, 95% CI 1.10-1.32, p=<0.001). The ACE D allele was significantly associated with increased susceptibility to IgA nephropathy compared to the I allele (OR 1.21, 95% CI 1.10-1.32, p<0.001), particularly in Asian populations.
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