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

Background. Conflicting results have implicated the angiotensin-converting enzyme (ACE) D allele in the progression of renal damage in patients with I gA nephropathy (IgAN). Most of these findings have been obtained by heterog eneous studies. Methods. We investigated the ACE insertion/deletion (I/D) gene polymorphism by polymerase chain reaction (PCR) amplification of genomic DNA in an ethn ically homogenous sample size of IgAN patients from Southern Italy. The ass ociation between ACE I/D gene polymorphism and the development of the disea se 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 greater than or equal to3 years according to the slope of the creatinine clearance against time, and in 221 patients wit h a follow-up of greater than or equal to1 year assessing by univariate and multivariate analyses of renal survival. These associations were further e stimated in a meta-analysis of seven studies retrieved in the Medline datab ase. The meta-analysis was performed according to the Mantel-Haenszel-Peto method when homogeneity of the studies was established using the chi (2) te st by Breslow-Day. Results. No difference in the ACE I/D gene distribution between patients an d controls and between patients with stable and those with deteriorating re nal function was found in our study. A meta-analysis performed separately f or Caucasian and Asian studies showed that the ACE IID gene polymorphism di d 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. respec tively) 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 interpretat ion of results from association studies enrolling heterogeneous populations . Further studies using new tests. which are free of the bias due to popula tion stratification and ethnicity. are warranted.