Linkage disequilibrium between S65C HFE mutation and HLA A29-B44 haplotype in Terceira Island, Azores

Couto, Ana Rita; Peixoto, Maria Manuela; Garrett, Francisco; Laranjeira, Francisco; Cipriano, Tania; Bruges-Armas, Jácome

doi:10.1016/s0198-8859(03)00052-1

Cited by 12 publications

(10 citation statements)

References 23 publications

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“…However, reports by Mura et al (1999) and Juan et al (2001) in French and Spanish individuals, respectively, consider frequency values of 1.9 and 3.0% for this mutation in healthy controls. More recently, in a study performed in the Terceira Island population (Azores), S65C mutation was found with an overall frequency of 2.1% in control individuals (Couto et al 2003). Similarly, we found an allelic frequency of 1.5% for S65C in the normal control group.…”

Section: Discussionsupporting

confidence: 76%

The role of HFE mutations on iron metabolism in beta-thalassemia carriers

et al. 2004

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Hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism characterized by increased iron absorption and progressive storage resulting in organ damage. HFE gene mutations C282Y and H63D are responsible for the majority of HH cases. A third HFE mutation, S65C, has been associated with the development of a mild form of hemochromatosis. The beta-thalassemia trait is characterized by mild, ineffective erythropoiesis that can induce excess iron absorption and ultimately lead to iron overload. The aim of this study was to evaluate the effect of genetic markers (HFE mutations C282Y, H63D, and S65C) on the iron status of beta-thalassemia carriers. A total of 101 individuals heterozygous for beta-thalassemia and 101 normal control individuals were studied. The allelic frequencies of C282Y (1.5 versus 3.5%), H63D (15.3 versus 18.3%), and S65C (1.0 versus 1.5%) did not differ significantly between beta-thalassemia carriers and normal controls. Serum iron (P=0.029) and transferrin saturation (P=0.009) were increased in betathalassemia carriers heterozygous for H63D mutation. The number of subjects carrying C282Y or S65C mutations was too low to conclude their effect on the iron status. These results suggest that the beta-thalassemia trait tends to be aggravated with the coinheritance of H63D mutation, even when present in heterozygosity.

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Section: Discussionsupporting

confidence: 76%

The role of HFE mutations on iron metabolism in beta-thalassemia carriers

et al. 2004

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“…However, the H63D and the S65C allele frequency in Madeira Island did not show significant differences with other Portuguese populations (p>0.1) [2320,296,28]. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 7 The low C282Y allele frequency found in Madeira Island is consistent with the northsouth decreasing cline that has been found in European countries and even in mainland Portugal [131,2320].…”

Section: Resultsmentioning

confidence: 73%

Prevalence of H63D, S65C, and C282Y hereditary hemochromatosis gene variants in Madeira Island (Portugal)

2010

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Hereditary HFE Hemochromatosis is an inherited disorder of iron metabolism that result from mutations in the HFE gene. Almost all patients with Hereditary Hemochromatosis show a C282Y mutation in homozygosity or in compound heterozygosity with H63D. Also, the mutation S65C has been shown to be associated to a milder iron overload. Since allele and genotype frequencies of these three variants of the HFE gene vary between populations, the determination of their prevalence in Madeira Island will clarify the population susceptibility to Hereditary Hemochromatosis. One hundred and fifty four samples from Madeira Island were genotyped for the three most common HFE gene mutations, H63D, C282Y and S65C, by Polymerase Chain Reaction followed by Restriction Fragment Length Polymorphism analysis. Results have shown a prevalence of 20.5%, 0.33% and 1% for H63D, C282Y and S65C, respectively. Accordingly to our estimates, both genotypes associated to Hereditary Hemochromatosis, C282Y homozygotes and C282/H63D compound heterozygotes, could be present in Madeira Island population in 1,648 individuals, which represents 0.65% of the total population.Response to Reviewers: . In this revised version we included the four references recommended by reviewers: Reviewer #1: The introduction to a large extent repeats well known facts about HFE hemochromatosis and should be shortened at least by 3/4 page. Authors: we shortened the introduction.Reviewer #1: There are several spelling errors. Authors: We made a spelling revision.Reviewer #1: In recent years, Annals of Hematology has published many papers on HFE haemochromatosis, among others by the authors Remacha AF, Pedersen P, Milman N, ect. I strongly suggest the authors make a screening on PubMed to identify these AOH papers and include them in the reference list. Authors: We added a paper from Remacha published in Annals of Hematology.

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“…However, it is unlikely that this could be responsible for more than a small proportion of cases, since other individuals had normal iron stores. Previous studies have demonstrated the rarity of hemochromatosis in this island population (35). Furthermore, the clinical and radiologic features seen in ectopic calcification are, in many aspects, different from the arthropathy of hemochromatosis (15).…”

Section: Bruges-armas Et Almentioning

confidence: 85%

Ectopic calcification among families in the Azores: Clinical and radiologic manifestations in families with diffuse idiopathic skeletal hyperostosis and chondrocalcinosis

Bruges-Armas¹,

Couto²,

Timms³

et al. 2006

Arthritis & Rheumatism

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Objective. Twelve families that were multiply affected with diffuse idiopathic skeletal hyperostosis (DISH) and/or chondrocalcinosis, were identified on the island of Terceira, The Azores, potentially supporting the hypothesis that the 2 disorders share common etiopathogenic factors. The present study was undertaken to investigate this hypothesis.Methods. One hundred three individuals from 12 unrelated families were assessed. Probands were identified from patients attending the Rheumatic Diseases Clinic, Hospital de Santo Espírito, in The Azores. Family members were assessed by rheumatologists and radiologists. Radiographs of all family members were obtained, including radiographs of the dorsolumbar spine, pelvis, knees, elbows, and wrists, and all cases were screened for known features of chondrocalcinosis.Results. Ectopic calcifications were identified in 70 patients. The most frequent symptoms or findings were as follows: axial pain, elbow, knee and metacarpophalangeal (MCP) joint pain, swelling, and/or deformity, and radiographic enthesopathic changes. Elbow and MCP joint periarticular calcifications were observed in 35 and 5 patients, respectively, and chondrocalcinosis was identified in 12 patients. Fifteen patients had sacroiliac disease (ankylosis or sclerosis) on computed tomography scans. Fifty-two patients could be classified as having definite (17%), probable (26%), or possible (31%) DISH. Concomitant DISH and chondrocalcinosis was diagnosed in 12 patients. Pyrophosphate crystals were identified from knee effusions in 13 patients. The pattern of disease transmission was compatible with an autosomal-dominant monogenic disease. The mean age at which symptoms developed was 38 years.Conclusion. These families may represent a familial type of pyrophosphate arthropathy with a phenotype that includes peripheral and axial enthesopathic calcifications. The concurrence of DISH and chondrocalcinosis suggests a shared pathogenic mechanism in the 2 conditions.

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Linkage disequilibrium between S65C HFE mutation and HLA A29-B44 haplotype in Terceira Island, Azores

Cited by 12 publications

References 23 publications

The role of HFE mutations on iron metabolism in beta-thalassemia carriers

The role of HFE mutations on iron metabolism in beta-thalassemia carriers

Prevalence of H63D, S65C, and C282Y hereditary hemochromatosis gene variants in Madeira Island (Portugal)

Ectopic calcification among families in the Azores: Clinical and radiologic manifestations in families with diffuse idiopathic skeletal hyperostosis and chondrocalcinosis

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