Key result
ACE gene polymorphisms were associated with an increased risk for diabetic nephropathy in a case-control analysis (e.g., OR 1.18 for rs4311-T), though this was not confirmed in family-based studies.
Why the study?
Are ACE gene polymorphisms associated with an increased risk of diabetic nephropathy in patients with type 1 diabetes?
Case-Control (n=3,780)
Yes
Are ACE gene polymorphisms associated with an increased risk of diabetic nephropathy in patients with type 1 diabetes?
Odds Ratio: 1.18 (95% CI 1.04–1.33)
ACE gene polymorphisms are associated with diabetic nephropathy in case-control analyses, but this association is not confirmed in family-based studies.
ACE polymorphisms should not inform nephropathy risk assessment in type 1 diabetes; case-control association leaves open need for replication.
Angiotensin 1-converting enzyme gene (ACE) is a risk factor for diabetic nephropathy (DN) in patients with type 1 diabetes. The selection of this candidate gene is supported by cross-sectional and follow-up studies, but no convincing family-based studies are available. Recruited were 1057 patients (with DN: persistent albuminuria with or without renal failure) and 1127 control subjects (long-standing [> or =15 yr] normoalbuminuric patients with type 1 diabetes) in Denmark, Finland, and France and 532 family trios that were composed of 244 trios with DN probands and 288 trios with non-DN probands. Five ACE polymorphisms were studied. In the case-control analysis, the rs1800764-C, rs4311-T, Insertion/deletion (I/D or rs1799752)-D, rs4366-G, and rs12449782-G alleles were associated with an increased risk for DN, homogeneously across populations, with allelic odds ratios of 1.11 (95% confidence interval 1.00 to 1.22), 1.18 (1.04 to 1.33), 1.13 (1.02 to 1.23), 1.10 (0.99 to 1.20), and 1.12 (1.01 to 1.23), respectively. Haplotype analysis further demonstrated that the haplotype defined by the D, rs4366_G and rs12449782_G alleles was associated with a greater risk for DN. Even though no significant allelic overtransmission to DN or non-DN probands was detected, the family-based study provided consistent results with the case-control analysis. In a large case-control study, it was shown that the ACE polymorphisms were associated with DN; these findings were not confirmed in a family-based association study. This study population is suitable to search for additional candidate genes for DN.
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Hadjadj et al. (2007) conducted a case-control in Diabetic nephropathy in type 1 diabetes (n=3,780). Angiotensin-converting enzyme (ACE) gene polymorphisms vs. Absence of risk alleles / normoalbuminuric controls was evaluated on Risk for diabetic nephropathy (OR 1.18, 95% CI 1.04 to 1.33). ACE gene polymorphisms were associated with an increased risk for diabetic nephropathy in a case-control analysis (e.g., OR 1.18 for rs4311-T), though this was not confirmed in family-based studies.
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