Elsevier

Kidney International

Volume 60, Issue 2, August 2001, Pages 732-740
Kidney International

Clinical Nephrology – Epidemiology – Clinical Trials
ACE gene polymorphism and IgA nephropathy: An ethnically homogeneous study and a meta-analysis

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ACE gene polymorphism and IgA nephropathy: An ethnically homogeneous study and a meta-analysis.

Background

Conflicting results have implicated the angiotensin-converting enzyme (ACE) D allele in the progression of renal damage in patients with IgA nephropathy (IgAN). Most of these findings have been obtained by heterogeneous studies.

Methods

We investigated the ACE insertion/deletion (I/D) gene polymorphism by polymerase chain reaction (PCR) amplification of genomic DNA in an ethnically homogenous sample size of IgAN patients from Southern Italy. The association between ACE I/D gene polymorphism and the development of the disease was examined in 247 biopsy-proven IgAN patients and 205 healthy subjects. The association with the progression of renal damage was evaluated in 136 patients with a follow-up of ≥3 years according to the slope of the creatinine clearance against time, and in 221 patients with a follow-up of ≥1 year assessing by univariate and multivariate analyses of renal survival. These associations were further estimated in a meta-analysis of seven studies retrieved in the Medline database. The meta-analysis was performed according to the Mantel-Haenszel-Peto method when homogeneity of the studies was established using the χ2 test by Breslow-Day.

Results

No difference in the ACE I/D gene distribution between patients and controls and between patients with stable and those with deteriorating renal function was found in our study. A meta-analysis performed separately for Caucasian and Asian studies showed that the ACE I/D gene polymorphism did not contribute to the genetic susceptibility of the development of IgAN (total OR 0.93, 95% CI, 0.71 to 1.23; and 0.95, 95% CI, 0.64 to 1.42, respectively) or the progression of the renal damage (total OR 1.12, 95% CI, 0.67 to 1.88; and 2.26, 95% CI, 0.75 to 6.79, respectively) in both groups.

Conclusions

Our study and meta-analysis suggest caution in the interpretation of results from association studies enrolling heterogeneous populations. Further studies using new tests, which are free of the bias due to population stratification and ethnicity, are warranted.

Keywords

angiotensin-converting enzyme gene
end-stage renal disease
RAS gene polymorphisms
progressive renal disease
primary glomerulonephritis

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