HNF4A genetic variants: role in diabetes.
OBJECTIVE
Variants in the hepatocyte nuclear factor 4alpha (HNF4A) gene play a role in the development of diabetes mellitus. Although genetic variation in and around HNF4A regulatory regions has received considerable attention, the significance of these variants in the common type 2 diabetes varies in the literature. This review will provide a general overview of recent genetic studies involving the evaluation of HNF4A as a contributor to the risk and pathophysiology of diabetes mellitus and related risk factors.


RESULTS
These studies report newly identified variants, evaluate previously reported polymorphisms that were associated with type 2 diabetes in several distinct populations with maturity-onset diabetes of the young, type 2 diabetes, gestational diabetes, and diabetes related risk factors, and propose a role for HNF4A in insulin secretion via the potassium ATP channel.


CONCLUSIONS
HNF4A variants identified so far appear to modestly contribute to predisposition for type 2 diabetes. Continued identification and especially functional characterization of variants, however, will be critical in future studies to enhance our understanding of the metabolic impact of this gene.
Love-Gregory
Latisha
L
Nutritional Sciences, Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Permutt
M Alan
MA
D017668:Age of Onset; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D016640:Diabetes, Gestational / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012307:Risk Factors
C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4