title: Prevalence of HFE mutations among the Thai population and correlation with iron loading in haemoglobin E disorder.
abstract: Co-inheritance of HFE mutations has a substantial role in iron overload in beta-thalassaemia carriers in north European populations where two HFE mutations, C282Y and H63D, are prevalent. In Thailand, there was little information about the allele frequency of HFE mutations. It is of interest to determine whether such determinants represent a potential risk in developing iron overload as nearly 40% of the Thai population carry either one of thalassaemia or haemoglobinpathy alleles. A total of 380 normal controls from five different regions including Bangkok were screened for the HFE C282Y, H63D and IVS5+1 G-->A alleles. In addition, 70 individuals with homozygous haemoglobin E (Hb EE) were also tested and their genotypes were correlated with levels of serum ferritin. H63D is the major HFE mutation found in the Thai population with an average allele frequency of 3% (range 1-5%). One individual was heterozygous for the splice site mutation IVS5 + 1 G --> A, and the C282Y allele was not detected. In the Hb EE group, five individuals had iron deficiency (ferritin <12 microg/L) and the remaining 65 individuals had a wide range of serum ferritin levels of 16-700 microg/L. Four individuals with Hb EE were heterozygous for the H63D allele. No significant difference in serum ferritin level was detected in this group with or without the HFE mutation (137.2 +/- 78 vs. 116.3 +/- 128 microg/L). HFE mutations are relatively uncommon among the Thai population, and the average allele frequency of the ancient H63D mutation is similar to that of other countries in this region. Because of their paucity, it appears that these alleles are less likely to be responsible for high ferritin levels and iron loading in individuals with Hb E related disorders.
authors.affiliation: Department of Pediatrics, Siriraj-Thalassaemia Research Program and WHO Collaborating Centre for the Control of Haemoglobinopathies, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. vip@hammer.imm.ox.ac.uk
authors.forename: Vip
authors.initials: V
authors.lastname: Viprakasit
authors.forename: Prin
authors.initials: P
authors.lastname: Vathesathokit
authors.forename: Worrawut
authors.initials: W
authors.lastname: Chinchang
authors.forename: Kalaya
authors.initials: K
authors.lastname: Tachavanich
authors.forename: Parichat
authors.initials: P
authors.lastname: Pung-Amritt
authors.forename: Victoria L C
authors.initials: VL
authors.lastname: Wimhurst
authors.forename: Pa-Thai
authors.initials: PT
authors.lastname: Yenchitsomanus
authors.forename: Alison T
authors.initials: AT
authors.lastname: Merryweather-Clarke
authors.forename: Voravarn S
authors.initials: VS
authors.lastname: Tanphaichitr
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005260:Female; D005293:Ferritins / Q000097:blood; D005787:Gene Frequency; D000071020:Hemochromatosis Protein; D006446:Hemoglobin E / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D000090463:Iron Deficiencies; D019190:Iron Overload / Q000097:blood / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D012326:RNA Splicing / Q000235:genetics; D013785:Thailand
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005293:Ferritins; D006446:Hemoglobin E