Document Detail


Glu298Asp and NOS4ab polymorphisms in diabetic nephropathy.
MedLine Citation:
PMID:  17101543     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND AIMS: The risk of diabetic nephropathy (DN) increases with increase in intraglomerular pressure, which may partly be regulated by nitric oxide (NO). NO-production can be affected by polymorphisms in the endothelial NO-synthase gene (NOS3), hyperglycaemia and smoking. We therefore studied association between DN and two polymorphisms in NOS3, Glu298Asp and NOS4ab, in Caucasian type 1 diabetes (T1D) patients. PATIENTS AND METHODS: A total of 1510 Finnish and Swedish T1D patients were included in a cross-sectional case-control study. Incipient DN was defined as an albumin excretion rate (AER) of 20-200 microg/min (n = 336). Overt DN = AER>200 microg/min or renal replacement therapy (n = 619). All patients with DN were considered as cases. The controls were T1D patients with diabetes duration 20 years, AER<20 microg/min and without antihypertensive treatment (n = 555). The genetic markers studied were a 27 bp repeat (NOS4ab) and Glu298Asp (rs1799983). RESULTS: Age at onset of diabetes, male sex, duration of diabetes, HbA1c, blood pressure and smoking were assessed as possible confounders in the logistic regression analysis, which showed that homozygosity for the Glu-allele of the Glu298Asp-polymorphism was independently associated with increased risk of DN (OR = 1.46; 95% CI = 1.12-1.91). The variables smoking (OR = 2.13; 95% CI = 1.63-2.78), male sex (OR = 1.61; 95% CI = 1.23-2.10), HbA1c (OR per % increase above upper limit of the normal reference range = 1.02; 95% CI = 1.02-1.03), systolic (OR = 1.05; 95% CI = 1.04-1.06) and diastolic blood pressure (OR = 1.04; 95% CI = 1.02-1.05) also significantly and independently increased the risk of DN when taking age at diabetes onset and diabetes duration into account. The NOS4 a-allele was not associated with DN. CONCLUSIONS: The Glu/Glu-genotype of the NOS3 Glu298Asp polymorphism may increase the risk of developing DN independently of other known risk factors.
Authors:
Anna Möllsten; Maija Wessman; Maria Svensson; Carol Forsblom; Maikki Parkkonen; Kerstin Brismar; Per-Henrik Groop; Gisela Dahlquist
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of medicine     Volume:  38     ISSN:  0785-3890     ISO Abbreviation:  Ann. Med.     Publication Date:  2006  
Date Detail:
Created Date:  2006-11-14     Completed Date:  2007-03-01     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8906388     Medline TA:  Ann Med     Country:  Sweden    
Other Details:
Languages:  eng     Pagination:  522-8     Citation Subset:  IM    
Affiliation:
Department of Clinical Sciences, Umeå University, Umeå, Sweden. anna.mollsten@pediatri.umu.se
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MeSH Terms
Descriptor/Qualifier:
Adult
Albuminuria / genetics*
Case-Control Studies
Cross-Sectional Studies
Diabetes Mellitus, Type 1 / complications,  genetics
Diabetic Nephropathies / genetics*
Female
Finland
Genetic Markers
Humans
Male
Middle Aged
Nitric Oxide Synthase Type III / genetics*
Polymorphism, Genetic / genetics*
Questionnaires
Risk Factors
Smoking / adverse effects*
Statistics as Topic
Sweden
Time Factors
Chemical
Reg. No./Substance:
0/Genetic Markers; EC 1.14.13.39/NOS3 protein, human; EC 1.14.13.39/Nitric Oxide Synthase Type III

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