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- Title
Impact of the hypoxia-inducible factor-1 α (HIF1A) Pro582Ser polymorphism on diabetes nephropathy.
- Authors
Gu HF; Zheng X; Abu Seman N; Gu T; Botusan IR; Sunkari VG; Lokman EF; Brismar K; Catrina SB; Gu, Harvest F; Zheng, Xiaowei; Abu Seman, Norhashimah; Gu, Tianwei; Botusan, Ileana Ruxandra; Sunkari, Vivekananda Gupta; Lokman, Ezarul Faradianna; Brismar, Kerstin; Catrina, Sergiu-Bogdan
- Abstract
<bold>Objective: </bold>Hypoxia plays a major pathogenic role in diabetic nephropathy (DN). We have investigated in this study the effect of hypoxia-inducible factor 1 α subunit (HIF1A) genetic polymorphisms on the development of DN.<bold>Research Design and Methods: </bold>In 1,165 American type 1 diabetic patients with and without DN selected from the Genetics of Kidneys in Diabetes (GoKinD) study, the HIF1A genetic polymorphisms were genotyped with TaqMan allelic discrimination. The regulation of HIF-1α in the kidneys of diabetic mice was appreciated by immunohistochemistry, and the effect HIF1A Pro582Ser polymorphism on HIF-1α sensitivity to glucose was evaluated in vitro.<bold>Results: </bold>We identified a protective association between HIF1A Pro582Ser polymorphism and DN in male subjects. We also provided mechanistic insights that HIF-1α is repressed in the medulla of diabetic mice despite hypoxia and that Pro582Ser polymorphism confers less sensitivity to the inhibitory effect of glucose during a hypoxic challenge.<bold>Conclusions: </bold>The current study demonstrates for the first time that HIF1A Pro582Ser polymorphism has an effect on DN, possibly by conferring a relative resistance to the repressive effect of glucose on HIF-1α.
- Publication
Diabetes Care, 2013, Vol 36, Issue 2, p415
- ISSN
0149-5992
- Publication type
journal article
- DOI
10.2337/dc12-1125