Genetic variation at the angiotensin-l converting enzyme locus and the risk for diabetic nephropathy: An update based on 53 studies and 17 791 subjects

Abstract

The association between the ACE insertion/deletion polymorphism and diabetic nephropathy has been debated for the past decade. To clarify this situation, we have updated our previous meta-analysis to include relevant studies published since 1994, yielding a total of 17 791 subjects from 53 studies. Cases (n = 9 556) were type 1 or 2 diabetic subjects with incipient or advanced diabetic nephropathy while controls (n = 8 235) were largely normoalbuminuric. No obvious publication bias was detected. Using a minimal case definition based on incipient diabetic nephropathy, II subjects had a 22% lower disease risk compared to D allele carriers (pooled OR = 0.78, 95%CI = 0.70-0.87). While there was a risk reduction among Caucasians with either type 1 or type 2 diabetes, the association was most marked among type 2 diabetic Asians (Chinese, Japanese, Koreans) (OR = 0.64, 95%CI = 0.51-0.80); this OR is significantly different from that obtained for type 2 diabetic Caucasians (OR = 0.89, 95%CI = 0.78-1.01) (p = 0.0105). With a stricter case definition based on advanced diabetic nephropathy, a comparable risk reduction of 19-30% was observed among the three subgroups. This reduction was statistically significant among type 2 diabetic Asians and Caucasians with type 1 but not type 2 diabetes. This updated meta-analysis strengthens the hypothesis that genetic variation at the ACE locus contributes to risk for diabetic nephropathy. Copyrigth © Sociedad Iberoamericana de Información Científica (SIIC), 2009.