Prevalence of HFE (hemochromatosis gene) mutations in unselected male patients with type 2 diabetes,☆☆

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Abstract

To assess the prevalence of mutations in the HFE (hemochromatosis) gene in unselected male patients with type 2 diabetes, we examined 220 white men without known diabetes and 220 age-matched white men with type 2 diabetes for mutations in the HFE gene. Nucleotide 845 (C282Y) and 187(H63D) alleles were amplified by polymerase chain reaction (PCR) with lymphocyte DNA. The PCR products were analyzed by restriction enzyme digestion. One of the 220 patients (0.45%) with diabetes was homozygous for the HFE 845A (C282Y) mutation and 25 (11.3%) were heterozygous for the same mutation, of whom 3 (1.3%) were compound heterozygotes also carrying the HFE 187G (H63D) mutation. These frequencies did not differ significantly from the control population without diabetes. There is no evidence that HFE mutations are found in excess in unselected male patients with type 2 diabetes, and there is no indication for a population-based search for an excess of these alleles in type 2 diabetes. (J Lab Clin Med 2000;135:170-3)

Section snippets

Patients

Two-hundred twenty white male patients with type 2 diabetes were recruited from the Bertram Diabetes Centre and from two large local general practice populations after ethical committee approval and written informed consent were obtained. Patients were studied if they were between 21 and 70 years of age at the time of diagnosis, had been taking oral hypoglycemics for at least 6 months, and had a body mass index of less than 32 kg/m2. Insulin treatment was not an exclusion as long as patients

Clinical features

Mean age of the patients with type 2 diabetes was 59.6 years (SD 8.2 years) and did not differ from the age-identical control subjects. Mean known duration of type 2 diabetes was 8.8 years (SD 6.5 years).

845A/845A mutant homozygote

One of the 220 patients (0.4%; 95% confidence interval 0% to 1.3%) and 1 of the 220 control subjects (0.4%; 95% confidence interval 0% to 1.3%) were homozygous for this mutation (P = 1.0).

Compound heterozygote 845G/845A with 187C/187G

Three of the 220 patients (1.4%) and 2 of the 220 control subjects (0.9%) were compound heterozygotes for

Discussion

We did not detect an excess of HFE mutations in patients with type 2 diabetes as compared with matched control subjects without known diabetes. This was despite biasing patient selection toward younger white male patients, a population most likely to clinically express these alleles, inasmuch as 15.9% of male patients with recognized HH have impaired glucose tolerance.13 Previous clinical studies in patients with diabetes have failed to detect an excess of HH as compared with the background

Acknowledgements

We thank Dr Henry Crawley and colleagues (Holt General Practice, Holt, England) and Dr David Pickersgill and colleagues (Birchwood Surgery, North Walsham, England) for their help with this study and for allowing access to their patients.

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    Reprint requests: M. J. Sampson, MD, Department of Diabetes and Endocrinology, Norfolk and Norwich Hospital, Brunswick Road, Norwich NR1 3SR UK.

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