Prevalence, characteristics, and prognostic significance of HFE gene mutations in type 2 diabetes: the Fremantle Diabetes Study.
OBJECTIVE
To examine the relationship between iron status, hereditary hemochromatosis (HFE) gene mutations, and clinical features and outcomes of type 2 diabetes in a well-characterized representative sample of community-based patients.


METHODS
HFE genotype data were available for 1,245 type 2 diabetic patients from the longitudinal observational Fremantle Diabetes Study (FDS), representing 96.2% of the total FDS type 2 diabetes cohort. Data were collected at recruitment between 1993 and 1996 and annually until the end of June 2001. Hospitalization and mortality data were available until the end of June 2006. The presence of the C282Y HFE mutation was determined in all subjects and H63D in C282Y heterozygotes. Fasting serum iron, transferrin, and ferritin were measured in all C282Y homozygotes and C282Y/H63D heterozygotes and in 286 randomly selected wild-type subjects. Multiple logistic regression analysis was performed to determine independent baseline associates of prevalent complications (myocardial infarction, cerebrovascular disease, retinopathy, neuropathy, and nephropathy), as was Cox proportional hazards modeling to determine predictors of incident complications and mortality.


RESULTS
Although there were expected positive associations between HFE gene mutations and serum iron and transferrin saturation, there were no independent positive associations between HFE gene status and either microvascular or macrovascular complications in cross-sectional and longitudinal analyses. HFE gene status did not independently predict cardiac or all-cause mortality. Measures of iron metabolism including serum ferritin were not associated with combined microvascular or macrovascular end points.


CONCLUSIONS
Directed screening for iron overload and/or HFE mutations appears unwarranted in patients with type 2 diabetes.
School of Medicine and Pharmacology, Fremantle Hospital, University of Western Australia, Fremantle, Australia. tdavis@cyllene.uwa.edu.au
Timothy M E
TM
Davis
John
J
Beilby
Wendy A
WA
Davis
John K
JK
Olynyk
Gary P
GP
Jeffrey
Enrico
E
Rossi
Conchita
C
Boyder
David G
DG
Bruce
D000368:Aged; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D005293:Ferritins / Q000097:blood; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000235:genetics; D008055:Lipids / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D011379:Prognosis
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008055:Lipids; D008565:Membrane Proteins; D005293:Ferritins; D007501:Iron