Haemochromatosis gene frequency in a control and diabetic Irish population

Kirk, L.; Bird, Jeremy; Ramadan, Samiha Hamdi Sayed; Samad, Abdus; Adebayo, Gani I.; Lourens, W.; Williams, John W

doi:10.1007/s11845-008-0248-6

Cited by 8 publications

(9 citation statements)

References 13 publications

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“…We did not find an association between H63D variant and diabetes in our cohort. This is consistent with a recent data from polish [19], Greek [20], British [21], American [22], Iranian [23], Australian [24], and Irish [25] populations. In contrast, one study in the Polish population found an increase in H63D allele carrier frequency in patients with diabetic nephropathy [26].…”

Section: Discussionsupporting

confidence: 93%

Frequency of the Hemochromatosis Gene (HFE) Variants in a Jordanian Arab Population and in Diabetics from the Same Region

2009

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Hereditary HFE-linked hemochromatosis is a frequent recessive disorder among individuals of northern European ancestry. The clinical characteristic of this disease is the gradual accumulation of iron in internal organs, which ultimately may lead to organ damage and death. Three allelic variants of HFE gene have been correlated with hereditary hemochromatosis: C282Y is significantly associated with hereditary hemochromatosis in populations of Celtic origin, H63D and S65C are associated with milder form of iron overload. In this study we performed mutation analysis to identify allele frequency of the three variants of HFE gene in Jordanian Arab population, to assess deviations of these frequencies from those detected elsewhere, and to determine if there is an increased frequency of these variants in a diabetic population (Type 2 diabetes) from the same area. DNA was extracted from blood samples of 440 individuals attending King Abdullah University Hospital for ambulatory services. We used polymerase chain reaction (PCR) to amplify exons 2 and 4 of the HFE gene then restriction fragment length polymorphism (RFLP) method to detect the variants. There were neither homozygous nor heterozygous for C282Y variant. For the H63D variant, 0.68% were homozygous and 21.1% were heterozygous. For the S65C variant, there were no homozygous and 0.23% were heterozygous. Allelic frequencies were, 0%, 11.25%, and 0.11% for C282Y, H63D, and S65C, respectively. Our samples were subdivided into two categories of type 2 diabetic (89 cases) and controls (blood donors, 204 cases) and compared with regard to the H63D variant. Both groups did not have homozygous H63D variant. H63D heterozygous in diabetics were 23.60% and in blood donor controls 22.55%. Allelic frequency of the mutant H63D allele was 11.80% in diabetics and 11.27% for the blood donor controls. This is the first study to show the frequency of the three hemochromatosis gene variants in Jordan with the interesting finding of no C282Y allele detected in 440 samples. Additionally, no significant difference was observed in H63D variant frequency in type 2 diabetics as compared to controls.

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Section: Discussionsupporting

confidence: 93%

Frequency of the Hemochromatosis Gene (HFE) Variants in a Jordanian Arab Population and in Diabetics from the Same Region

2009

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“…Lower prevalence estimates have been reported from control populations in northern Spain (Catalonia) [69], among Basques in Guipuzcoa, Spain [70], and in central Italy [71]. The combined prevalence of C282Y homozygosity in 404 control subjects in Northern Ireland [72] and 249 control subjects in the northwestern Republic of Ireland [73] was 0.012 [95% confidence interval 0.006, 0.025]. Penetrance of iron overload phenotypes is variable and often greater in men [64].…”

Section: Hfe Coding Region Mutationsmentioning

confidence: 99%

HFE gene: Structure, function, mutations, and associated iron abnormalities

Barton

Edwards

Acton

2015

Gene

111

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The hemochromatosis gene HFE was discovered in 1996, more than a century after clinical and pathologic manifestations of hemochromatosis were reported. Linked to the major histocompatibility complex (MHC) on chromosome 6p, HFE encodes the MHC class I-like protein HFE that binds beta-2 microglobulin. HFE influences iron absorption by modulating the expression of hepcidin, the main controller of iron metabolism. Common HFE mutations account for ~90% of hemochromatosis phenotypes in whites of western European descent. We review HFE mapping and cloning, structure, promoters and controllers, and coding region mutations, HFE protein structure, cell and tissue expression and function, mouse Hfe knockouts and knockins, and HFE mutations in other mammals with iron overload. We describe the pertinence of HFE and HFE to mechanisms of iron homeostasis, the origin and fixation of HFE polymorphisms in European and other populations, and the genetic and biochemical basis of HFE hemochromatosis and iron overload.

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“…The frequency was also lower than in Norway 0.09 (14) and possibly also than in Denmark 0.06 (36), but the difference was not significant. These observations suggest a west to east falling gradient through the north of Europe from Ireland (7–10) through Scotland (11) to Scandinavia, a decline similar to other genes like the phenylketonuria mutation (5, 37).…”

Section: Discussionmentioning

confidence: 89%

“…There is still some uncertainty regarding the age and origin of the C282Y mutation because the methods used for such estimates remain uncertain (5, 17). Most studies suggest that the common ancestor carried HLA‐A3‐B7 (4, 5) or A3‐B14 (8, 18, 19), and the very high C282Y frequency in Ireland (5, 7–10), Scotland (11), Wales (30) and Brittany (4) has suggested an Irish Celtic origin (12, 13). Recently, similarly high frequencies were reported from central Norway (14), which might support a Viking origin (15–17).…”

Section: Discussionmentioning

confidence: 99%

“…Although it is unclear when and where this person lived (5), most of the descendants are found along north Atlantic coast lines and in countries with emigrants of this origin (5, 6). The peak C282Y frequency is met in Ireland (7–10) and Scotland (11), which has suggested an Irish Celtic origin (12, 13), but a high frequency has also been reported from Scandinavia (14), suggesting a Viking origin (7, 15–17). An Irish origin with a further spread by the Vikings has also been proposed (13).…”

mentioning

confidence: 96%

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Was the C282Y mutation an Irish Gaelic mutation that the Vikings helped disseminate?*

Olsson

Konar

Dufva

et al. 2010

European Journal of Haematology

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Haemochromatosis gene frequency in a control and diabetic Irish population

Abstract: For the three haemochromatosis mutations, there was no significant difference between the control group and the diabetic populations.

Cited by 8 publications

References 13 publications

Frequency of the Hemochromatosis Gene (HFE) Variants in a Jordanian Arab Population and in Diabetics from the Same Region

Frequency of the Hemochromatosis Gene (HFE) Variants in a Jordanian Arab Population and in Diabetics from the Same Region

HFE gene: Structure, function, mutations, and associated iron abnormalities

Was the C282Y mutation an Irish Gaelic mutation that the Vikings helped disseminate?*

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