Impact of the hypoxia-inducible factor-1 ? (HIF1A) Pro582Ser polymorphism on diabetes nephropathy.

ABSTRACT:

Objective

Hypoxia plays a major pathogenic role in diabetic nephropathy (DN). We have investigated in this study the effect of hypoxia-inducible factor 1 ? subunit (HIF1A) genetic polymorphisms on the development of DN.

Research design and methods

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-1? in the kidneys of diabetic mice was appreciated by immunohistochemistry, and the effect HIF1A Pro582Ser polymorphism on HIF-1? sensitivity to glucose was evaluated in vitro.

Results

We identified a protective association between HIF1A Pro582Ser polymorphism and DN in male subjects. We also provided mechanistic insights that HIF-1? 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.

Conclusions

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-1?.

SUBMITTER: Gu HF 

PROVIDER: S-EPMC3554309 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature