Population-based analysis of the frequency of HFE gene polymorphisms: Correlation with the susceptibility to develop hereditary hemochromatosis

Katsarou,Martha‑Spyridoula; Latsi,Rosana; Papasavva,Maria; Demertzis,Nikolaos; Kalogridis,Thodoris; Tsatsakis,Aristides  M.; Spandidos,Demetrios  A.; Drakoulis,Nikolaos

doi:10.3892/mmr.2016.5317

July-2016 Volume 14 Issue 1

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

July-2016 Volume 14 Issue 1

Full Size Image

Article Open Access

Population-based analysis of the frequency of HFE gene polymorphisms: Correlation with the susceptibility to develop hereditary hemochromatosis

Authors:
- Martha‑Spyridoula Katsarou
- Rosana Latsi
- Maria Papasavva
- Nikolaos Demertzis
- Thodoris Kalogridis
- Aristides M. Tsatsakis
- Demetrios A. Spandidos
- Nikolaos Drakoulis
View Affiliations / Copyright

Affiliations: Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens 157 71, Greece, Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, Heraklion 71003, Greece, Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion 71409, Greece

Copyright: © Katsarou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 630-636
|
Published online on: May 20, 2016

https://doi.org/10.3892/mmr.2016.5317
Expand metrics +

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.

View Figures

View References

1	Boron W and Boulpaep EL: Blood physiology. Medical Physiology: A Cellular and Molecular Approach. Koutsileiris M: 3. Greek Edition. Paschalidis Medical Editions; Athens; pp. p16532006
2	Vander A, Sherman J, Luciano D and Tsakopoulos M: Human Physiology: The Mechanisms of Body Function. 2. 8th edition. Paschalidis Medical Editions; Athens: pp. p516pp. p7502011
3	Damjanov I: Pathophysiology. Greek Edition. Parisianos Scientific Editions; Athens: pp. 448–449. pp. 512–515. 2011
4	Genetics Home Reference. http://ghr.nlm.nih.gov/gene/HFE. Accessed April 1, 2016.
5	Tandara L and Salamunic I: Iron metabolism: Current facts and future directions. Biochem Med Zagreb. 22:311–328. 2012. View Article : Google Scholar : PubMed/NCBI
6	Yen AW, Fancher TL and Bowlus CL: Revisiting hereditary hemochromatosis: Current concepts and progress. Am J Med. 119:391–399. 2006. View Article : Google Scholar : PubMed/NCBI
7	Puntarulo S: Iron, oxidative stress and human health. Mol Aspects Med. 26:299–312. 2005. View Article : Google Scholar : PubMed/NCBI
8	von Recklinghausen FD: Uber haemochromatose. Tageblatt Versammlung Dtsche. Naturforscher Arzte Heidelberg. 62:324–325. 1889.
9	Mura C, Raguenes O and Férec C: HFE mutations analysis in 711 hemochromatosis probands: Evidence for S65C implication in mild form of hemochromatosis. Blood. 93:2502–2505. 1999.PubMed/NCBI
10	Merryweather-Clarke AT, Cadet E, Bomford A, Capron D, Viprakasit V, Miller A, McHugh PJ, Chapman RW, Pointon JJ, Wimhurst VL, et al: Digenic inheritance of mutations in HAMP and HFE results in different types of haemochromatosis. Hum Mol Genet. 12:2241–2247. 2003. View Article : Google Scholar : PubMed/NCBI
11	Lyon E and Frank EL: Hereditary hemochromatosis since discovery of the HFE gene. Clin Chem. 47:1147–1156. 2001.PubMed/NCBI
12	Gallego CJ, Burt A, Sundaresan AS, Ye Z, Shaw C, Crosslin DR, Crane PK, Fullerton SM, Hansen K, Carrell D, et al: Penetrance of Hemochromatosis in HFE Genotypes Resulting in p.Cys282Tyr and p.[Cys282Tyr];[His63Asp] in the eMERGE Network. Am J Hum Genet. 97:512–520. 2015. View Article : Google Scholar : PubMed/NCBI
13	Crownover BK and Covey CJ: Hereditary hemochromatosis. Am Fam Physician. 87:183–190. 2013.PubMed/NCBI
14	Hentze MW, Muckenthaler MU, Galy B and Camaschella C: Two to tango: Regulation of mammalian iron metabolism. Cell. 142:24–38. 2010. View Article : Google Scholar : PubMed/NCBI
15	Ganz T: Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood. 102:783–788. 2003. View Article : Google Scholar : PubMed/NCBI
16	Hanson EH, Imperatore G and Burke W: HFE gene and hereditary hemochromatosis: a HuGE review. Human Genome Epidemiology. Am J Epidemiol. 154:193–206. 2001. View Article : Google Scholar : PubMed/NCBI
17	Hutchinson C, Geissler CA, Powell JJ and Bomford A: Proton pump inhibitors suppress absorption of dietary non-haem iron in hereditary haemochromatosis. Gut. 56:1291–1295. 2007. View Article : Google Scholar : PubMed/NCBI
18	Namipashaki A, Razaghi-Moghadam Z and Ansari-Pour N: The Essentiality of Reporting Hardy-Weinberg Equilibrium Calculations in Population-Based Genetic Association Studies. Cell J. 17:187–192. 2015.PubMed/NCBI
19	Wigginton JE, Cutler DJ and Abecasis GR: A note on exact tests of Hardy-Weinberg equilibrium. Am J Hum Genet. 76:887–893. 2005. View Article : Google Scholar : PubMed/NCBI
20	Franchini M and Veneri D: Recent advances in hereditary hemochromatosis. Ann Hematol. 84:347–352. 2005. View Article : Google Scholar : PubMed/NCBI
21	Zhou T, Neubert H, Liu DY, Liu ZD, Ma YM, Kong XL, Luo W, Mark S and Hider RC: Iron binding dendrimers: a novel approach for the treatment of haemochromatosis. J Med Chem. 49:4171–4182. 2006. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Population-based analysis of the frequency of HFE gene polymorphisms: Correlation with the susceptibility to develop hereditary hemochromatosis

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Related Articles