期刊
DIABETIC MEDICINE
卷 27, 期 10, 页码 1188-1194出版社
WILEY-BLACKWELL PUBLISHING, INC
DOI: 10.1111/j.1464-5491.2010.03097.x
关键词
ACE; AGTR1; association; diabetes; nephropathy
资金
- Research and Development Office Northern Ireland
- Northern Ireland Kidney Research Fund
- Economic and Social Research Council [ES/G007438/1] Funding Source: researchfish
- Public Health Agency [STL/3714/07] Funding Source: researchfish
- ESRC [ES/G007438/1] Funding Source: UKRI
Background Polymorphisms in ACE and AGTR1 genes have been assessed in multiple studies for association with diabetic nephropathy; however, results are conflicting. The ACE2 gene has not been studied extensively for association with diabetic nephropathy. Methods We investigated variants in ACE, ACE2 and AGTR1 for association with nephropathy in a case-control group (1467 participants with Type 1 diabetes, case subjects n = 718; control subjects n = 749) of white descent with grandparents born in the British Isles. All recruited individuals were carefully phenotyped and genotyping was performed using Sequenom, Taqman and gel electrophoresis methods. The chi(2)-test for contingency tables was used to compare genotype and allele frequencies in case and control groups. Results No departure from Hardy-Weinberg equilibrium was observed in cases or controls. Two variants within the ACE gene (rs4293, P(allelic) = 0.02, P(genotypic) = 0.008; rs4309, P(allelic) = 0.02, P(genotypic) = 0.01) were significantly associated with nephropathy at the 5% level. No variant remained statistically significant following adjustment for multiple comparisons. No single nucleotide polymorphisms in the ACE2 or AGTR1 genes were significantly associated with nephropathy when analysed either by genotype or allele frequencies. Conclusions Our independent case-control study provides no evidence that common variants in ACE, ACE2 and AGTR1 play a major role in genetic susceptibility to diabetic nephropathy in a white population with Type 1 diabetes.
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