title: Population-based analysis of the frequency of HFE gene polymorphisms: Correlation with the susceptibility to develop hereditary hemochromatosis.
abstract: Hereditary hemochromatosis (HH) is an autosomal recessive genetic disease, characterized by increased dietary iron absorption. Due to the absence of an effective excretory mechanism, the excess iron in the body may accumulate resulting in toxic effects. The HFE gene also affects the activity of hepcidin, a hormone which acts as a negative regulator of iron metabolism. In this study, we performed a population-based analysis of the distribution of three hemochromatosis-related polymorphisms in the HFE gene (rs1800562, rs1799945 and rs1800730). DNA from 1,446 non‑related individuals of Greek ethnicity was collected and analyzed, either from whole blood or buccal swabs. The frequency distribution of these HFE gene polymorphisms was then determined. The results revealed that in our Greek population cohort (gr) the frequencies of each polymorphism were as follows: rs1800562: GG (wild‑type)=97.0%, GA=1.5%, AA=1.5%; rs1799945: CC (wild‑type)=74.4%, CG=23.4%, GG=2.2%; rs1800730: AA (wild‑type)=98.1%, AT=1.5% and TT=0.4%. No association between the HFE polymorphisms rs1800562, rs1799945 and rs1800730 and gender could be established. As regards the rs1800562 polymorphism, the A allele (mutant) was ~1.8‑fold more frequent in the European population (eur) than in the Greek population [(gr)=2,3%<(eur)=4%]. As for the rs1799945 polymorphism, the G allele (mutant) was 1.2‑fold more frequent in the European population than in the Greek population [(gr)=13,9%<(eur)=17%]. As regards the rs1800730 polymorphism, the T allele (mutant) was ~1.7‑fold more frequent in the European population than in the Greek population [(gr)=1.2%<(eur)=2%]. However, these pathogenic mutations were found more frequently in the Greek population compared to the global population (gl) [rs1800562: (gl)=1%<(gr)=2,3%; rs1799945: (gl)=7%<(gr)=13,9%; rs1800730: (gl)=<1%<(gr)=1.2%]. This suggests that the Greek population may differ genetically from the northern European population, due to influences from neighboring Asian and African populations. These findings also suggest that there is no gender-associated inheritance of these polymorphisms, and gender-specific symptoms appear as a result of independent biological processes. Thus, the early detection of the tendency towards iron accumulation may be achieved by the genotypic analysis of the polymorphisms that may contribute to the development of the hemochromatosis.
authors.affiliation: Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens 157 71, Greece.
authors.forename: Martha-Spyridoula
authors.initials: MS
authors.lastname: Katsarou
authors.affiliation: Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens 157 71, Greece.
authors.forename: Rosana
authors.initials: R
authors.lastname: Latsi
authors.affiliation: Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens 157 71, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Papasavva
authors.affiliation: Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens 157 71, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Demertzis
authors.affiliation: Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens 157 71, Greece.
authors.forename: Thodoris
authors.initials: T
authors.lastname: Kalogridis
authors.affiliation: Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, Heraklion 71003, Greece.
authors.forename: Aristides M
authors.initials: AM
authors.lastname: Tsatsakis
authors.affiliation: Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion 71409, Greece.
authors.forename: Demetrios A
authors.initials: DA
authors.lastname: Spandidos
authors.affiliation: Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens 157 71, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Drakoulis
mesh_terms: D000483:Alleles; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006115:Greece / Q000453:epidemiology; D006432:Hemochromatosis / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D000071020:Hemochromatosis Protein / Q000235:genetics*; D006801:Humans; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D044382:Population Groups / Q000235:genetics; D011159:Population Surveillance
chemical_list: D000071020:Hemochromatosis Protein