Investigation of the human ANP gene in type 1 diabetic nephropathy: case-control and follow-up studies.
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.
Roussel
Ronan
R
Diabétologie, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, 46 rue Henri Huchard, 75877 Paris Cedex 18, France. ronan.roussel@polytechnique.org
Trégouët
David-Alexandre
DA
Hadjadj
Samy
S
Jeunemaître
Xavier
X
Marre
Michel
M
D000328:Adult; D000483:Alleles; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003596:Cytosine; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D016019:Survival Analysis; D013941:Thymine
D009320:Atrial Natriuretic Factor; D003596:Cytosine; D013941:Thymine