Abstract
This is an epidemiologic study of the Slovak population with the aim of determining the frequencies of three hemochromatosis gene (HFE) variants C282Y, H63D and S65C known to be associated with manifestation of hereditary hemochromatosis and to assess deviations of these frequencies from those reported elsewhere. Mutations were detected in 359 ethnic Slovaks by real-time PCR assay based on TaqMan technology. The allelic frequencies were 4.03% for C282Y, 12.67% for H63D and 1.25% for S65C mutation. We observed 0.28% of C282Y/C282Y homozygotes, 3.34% H63D/H63D homozygotes, 0.84% of C282Y/H63D compound heterozygotes and 0.56% of H63D/S65C compound heterozygotes. This is the first time the frequencies of H63D and S65C mutations have been reported in the general population in Slovakia. The observed allelic frequencies are consistent with the previous studies of Slavic and Central European populations.
[1] Bothwell T.H., MacPhail A.P., Hereditary hemochromatosis: etiologic, pathologic, and clinical aspects, Semin Hematol 1998,35(1),55–71 Search in Google Scholar
[2] Hanson E.H., Imperatore G., Burke W., HFE gene and hereditary hemochromatosis: a HuGE review. Human Genome Epidemiology, Am J Epidemiol 2001,154(3),193–206 http://dx.doi.org/10.1093/aje/154.3.19310.1093/aje/154.3.193Search in Google Scholar
[3] Frazer D.M., Anderson G.J., Iron imports. I. Intestinal iron absorption and its regulation, Am J Physiol Gastrointest Liver Physiol 2005,289(4),G631–635 10.1152/ajpgi.00220.2005Search in Google Scholar
[4] Moirand R., Jouanolle A.M., Brissot P., Le Gall J.Y., David V., Deugnier Y., Phenotypic expression of HFE mutations: a French study of 1110 unrelated ironoverloaded patients and relatives, Gastroenterology 1999,116(2),372–377 http://dx.doi.org/10.1016/S0016-5085(99)70134-410.1016/S0016-5085(99)70134-4Search in Google Scholar
[5] Brissot P., Moirand R., Jouanolle A.M., Guyader D., Le Gall J.Y., Deugnier Y., et al., A genotypic study of 217 unrelated probands diagnosed as “genetic hemochromatosis” on “classical” phenotypic criteria, J Hepatol 1999,30(4),588–593 http://dx.doi.org/10.1016/S0168-8278(99)80188-310.1016/S0168-8278(99)80188-3Search in Google Scholar
[6] Mura C., Raguenes O., Ferec C., HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C implication in mild form of hemochromatosis, Blood 1999,93(8),2502–2505 10.1182/blood.V93.8.2502.408k27_2502_2505Search in Google Scholar
[7] Le Gac G., Ferec C., The molecular genetics of haemochromatosis, Eur J Hum Genet 2005,13(11),1172–1185 http://dx.doi.org/10.1038/sj.ejhg.520149010.1038/sj.ejhg.5201490Search in Google Scholar
[8] Asberg A., Thorstensen K., Hveem K., Bjerve K.S., Hereditary hemochromatosis: the clinical significance of the S65C mutation, Genet Test 2002,6(1),59–62 http://dx.doi.org/10.1089/10906570276009393310.1089/109065702760093933Search in Google Scholar
[9] Lucotte G., Dieterlen F., A European allele map of the C282Y mutation of hemochromatosis: Celtic versus Viking origin of the mutation?, Blood Cells Mol Dis 2003,31(2),262–267 http://dx.doi.org/10.1016/S1079-9796(03)00133-510.1016/S1079-9796(03)00133-5Search in Google Scholar
[10] Rochette J., Pointon J.J., Fisher C.A., Perera G., Arambepola M., Arichchi D.S., et al., Multicentric origin of hemochromatosis gene (HFE) mutations, Am J Hum Genet 1999,64(4),1056–1062 http://dx.doi.org/10.1086/30231810.1086/302318Search in Google Scholar PubMed PubMed Central
[11] Merryweather-Clarke A.T., Pointon J.J., Jouanolle A.M., Rochette J., Robson K.J., Geography of HFE C282Y and H63D mutations, Genet Test 2000,4(2),183–198 http://dx.doi.org/10.1089/1090657005011490210.1089/10906570050114902Search in Google Scholar PubMed
[12] Ristic S., Makuc J., Starcevic N., Logar N., Brajenovic-Milic B., Stepec S., et al., Hemochromatosis gene mutations in the Croatian and Slovenian populations, Clin Genet 2003,64(5),444–446 http://dx.doi.org/10.1034/j.1399-0004.2003.00169.x10.1034/j.1399-0004.2003.00169.xSearch in Google Scholar
[13] Cimburova M., Putova I., Provaznikova H., Pinterova D., Horak J., S65C and other mutations in the haemochromatosis gene in the Czech population, Folia Biol (Praha) 2005,51(6),172–176 Search in Google Scholar
[14] Pedersen P., Melsen G.V., Milman N., Frequencies of the haemochromatosis gene (HFE) variants C282Y, H63D and S65C in 6,020 ethnic Danish men, Ann Hematol 2008,87(9),735–740 http://dx.doi.org/10.1007/s00277-008-0506-810.1007/s00277-008-0506-8Search in Google Scholar
[15] Edwards C.Q., Griffen L.M., Goldgar D., Drummond C., Skolnick M.H., Kushner J.P., Prevalence of hemochromatosis among 11,065 presumably healthy blood donors, N Engl J Med 1988,318(21),1355–1362 http://dx.doi.org/10.1056/NEJM19880526318210310.1056/NEJM198805263182103Search in Google Scholar
[16] Cukjati M., Vaupotic T., Rupreht R., Curin-Serbec V., Prevalence of H63D, S65C and C282Y hereditary hemochromatosis gene mutations in Slovenian population by an improved high-throughput genotyping assay, BMC Med Genet 2007,8,69 http://dx.doi.org/10.1186/1471-2350-8-6910.1186/1471-2350-8-69Search in Google Scholar
[17] Datz C., Lalloz M.R., Vogel W., Graziadei I., Hackl F., Vautier G., et al., Predominance of the HLA-H Cys282Tyr mutation in Austrian patients with genetic haemochromatosis, J Hepatol 1997,27(5),773–779 http://dx.doi.org/10.1016/S0168-8278(97)80312-110.1016/S0168-8278(97)80312-1Search in Google Scholar
[18] Terzic R., Sehic A., Teran N., Terzic I., Peterlin B., Frequency of HFE gene mutations C282Y and H63D in Bosnia and Herzegovina, Coll Antropol 2006,30(3),555–557 Search in Google Scholar
[19] Raszeja-Wyszomirska J., Kurzawski G., Suchy J., Zawada I., Lubinski J., Milkiewicz P., Frequency of mutations related to hereditary haemochromatosis in northwestern Poland, J Appl Genet 2008,49(1),105–107 http://dx.doi.org/10.1007/BF0319525510.1007/BF03195255Search in Google Scholar PubMed
[20] Moczulski D.K., Grzeszczak W., Gawlik B., Frequency of the hemochromatosis C282Y and H63D mutations in a Polish population of Slavic origin, Med Sci Monit 2001,7(3),441–443 Search in Google Scholar
[21] Zlocha J., Kovacs L., Pozgayova S., Kupcova V., Durinova S., [Molecular genetic diagnostics and screening of hereditary hemochromatosis], Vnitr Lek 2006,52(6),602–608, (In Slovak) Search in Google Scholar
[22] Saric M., Zamurovic L., Keckarevic-Markovic M., Keckarevic D., Stevanovic M., Savic-Pavicevic D., et al., Frequency of the hemochromatosis gene mutations in the population of Serbia and Montenegro, Clin Genet 2006,70(2),170–172 http://dx.doi.org/10.1111/j.1399-0004.2006.00655.x10.1111/j.1399-0004.2006.00655.xSearch in Google Scholar PubMed
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