Impact of the hypoxia-inducible factor-1 α (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 α 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-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. RESULTS: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. 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-1α.

journal_name

Diabetes Care

journal_title

Diabetes care

authors

Gu HF,Zheng X,Abu Seman N,Gu T,Botusan IR,Sunkari VG,Lokman EF,Brismar K,Catrina SB

doi

10.2337/dc12-1125

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

415-21

issue

2

eissn

0149-5992

issn

1935-5548

pii

dc12-1125

journal_volume

36

pub_type

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