| Genotyping and functional analysis of a polymorphic (CCTTT)(n) repeat of NOS2A in diabetic retinopathy. | |
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MedLine Citation:
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PMID: 10506586 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Accumulating evidence shows that the severity and rapidity of onset of diabetic retinopathy are influenced by genetic factors. Expression of the nitric oxide synthases is altered in the retinal vasculature in the early stages of diabetic retinopathy. We analyzed the allele distribution of a polymorphic pentanucleotide repeat within the 5' upstream promoter region of the NOS2A gene in samples of diabetic patients. In diabetic patients from Northern Ireland, the 14-repeat allele of the NOS2A marker was significantly associated with the absence of diabetic retinopathy. Carriers of this repeat had 0.21-fold the relative risk of developing diabetic retinopathy than noncarriers of this allele. They also had significantly fewer renal and cardiovascular complications. The ability of differing numbers of (CCTTT)(n) pentanucleotide repeats to induce transcription of the NOS2A gene was analyzed using a luciferase reporter gene assay in transfected colonic carcinoma cells. Interleukin 1beta (IL-1beta) induction was most effective in constructs carrying the 14-repeat allele. When cells were incubated in 25 mM glucose to mimic the diabetic state, IL-1beta induction was inhibited in all cases, but to a significantly lesser extent with the 14-repeat allele. These unique properties of the 14-repeat allele may confer selective advantages in diabetic individuals, which may delay or prevent microvascular complications of diabetes. |
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Authors:
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K M Warpeha; W Xu; L Liu; I G Charles; C C Patterson; F Ah-Fat; S Harding; P M Hart; U Chakravarthy; A E Hughes |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 13 ISSN: 0892-6638 ISO Abbreviation: FASEB J. Publication Date: 1999 Oct |
Date Detail:
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Created Date: 1999-11-02 Completed Date: 1999-11-02 Revised Date: 2012-02-15 |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1825-32 Citation Subset: IM |
Affiliation:
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Department of Medical Genetics, Ophthalmology and Vision Sciences, Queen's University, Belfast, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Base Sequence Diabetes Complications Diabetes Mellitus / genetics* Diabetes Mellitus, Type 1 / complications, genetics Diabetes Mellitus, Type 2 / complications, genetics Diabetic Retinopathy / genetics* Female Gene Expression Regulation, Enzymologic* Glucose / pharmacology Humans Interleukin-1 / pharmacology Male Microsatellite Repeats* Middle Aged Molecular Sequence Data Nitric Oxide Synthase / genetics* Nitric Oxide Synthase Type II Polymorphism, Genetic* |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-1; 50-99-7/Glucose; EC 1.14.13.39/NOS2 protein, human; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type II |
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