Abstract
The atrial natriuretic peptide gene (PND) is a candidate gene for diabetic nephropathy. We systematically analyzed five nonsynonymous PND polymorphisms and tested the association of genotype and haplotype distributions with diabetic nephropathy in a cross-sectional study and a 6-year follow-up study (489 and 301 type 1 diabetic patients, respectively). For this purpose, a new maximum-likelihood method dealing with haplotype-based association analysis for survival data was developed. None of the genotypes or haplotypes were associated with the disease in the case-control study. In the follow-up study, C708T and T2238C showed a weak association with disease progression, but T2238C was strongly associated with progression in poorly controlled subjects (mean HbA(1c) during follow-up was more than the median value [8.5%]; log-rank [TC or CC versus TT], P = 0.007; adjusted hazard ratio, TC or CC versus TT, 2.28, 95% CI 1.10-4.74; P = 0.027). The raw effect of the 2238C allele (hazard risk ratio 1.93, 95% CI 1.15-3.24; P = 0.012) was further confirmed by the haplotype analysis, suggesting that the 2238C allele of PND may affect the course of nephropathy in inadequately controlled type 1 diabetic patients.
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