HFE gene mutations and iron status of Brazilian blood donors

Santos, Paulo Caleb Júnior Lima; Cançado, Rodolfo Delfini; Terada, Cristiane T.; Rostelato, S.; Gonzales, I.; Hirata, Rosário Dominguez Crespo; Hirata, Mário Hiroyuki; Chiattone, Carlos S.; Guerra-Shinohara, Elvira María

doi:10.1590/s0100-879x2009007500031

Cited by 18 publications

(14 citation statements)

References 33 publications

(7 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In Northern European populations, the HFE p.Cys282Tyr homozygous genotype is particularly common (1 in 200–300 healthy subjects) and the HFE 282Tyr allele frequency is high (5.1 to 8.2%) [9]. In contrast, in countries with racial/ethnic heterogeneity from South America, Asia and Africa a lower prevalence of HH have been observed, and an increased number of patients with primary iron overload do not carry the p.Cys282Tyr/p.Cys282Tyr or p.Cys282Tyr/p.His63Asp genotypes [10,11] (for example, a minor allele frequency of p.Cys282Tyr allele of 2.3% is observed in Brazilian blood donors) [12,13]. …”

Section: Introductionmentioning

confidence: 99%

Molecular Diagnostic and Pathogenesis of Hereditary Hemochromatosis

Santos

Pereira

2012

IJMS

View full text Add to dashboard Cite

Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by enhanced intestinal absorption of dietary iron. Without therapeutic intervention, iron overload leads to multiple organ damage such as liver cirrhosis, cardiomyopathy, diabetes, arthritis, hypogonadism and skin pigmentation. Most HH patients carry HFE mutant genotypes: homozygosity for p.Cys282Tyr or p.Cys282Tyr/p.His63Asp compound heterozygosity. In addition to HFE gene, mutations in the genes that encode hemojuvelin (HJV), hepcidin (HAMP), transferrin receptor 2 (TFR2) and ferroportin (SLC40A1) have been associated with regulation of iron homeostasis and development of HH. The aim of this review was to identify the main gene mutations involved in the pathogenesis of type 1, 2, 3 and 4 HH and their genetic testing indication. HFE testing for the two main mutations (p.Cys282Tyr and p.His63Asp) should be performed in all patients with primary iron overload and unexplained increased transferrin saturation and/or serum ferritin values. The evaluation of the HJV p.Gly320Val mutation must be the molecular test of choice in suspected patients with juvenile hemochromatosis with less than 30 years and cardiac or endocrine manifestations. In conclusion, HH is an example that genetic testing can, in addition to performing the differential diagnostic with secondary iron overload, lead to more adequate and faster treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

Molecular Diagnostic and Pathogenesis of Hereditary Hemochromatosis

Santos

Pereira

2012

IJMS

View full text Add to dashboard Cite

show abstract

“…The prevalence of the HFE gene alleles C282Y, H63D and S65C in the general healthy population in Brazil ranges from 1.15-2.19%, 9.54-14.57 and 0.31-1%, respectively. At the same time, for the patient group, the alleles range from 7.36-50% for C282Y, 6.25-26.59% for H63D and 0-2.23% for S65C (Bueno et al, 2006;Oliveira et al, 2006;Cançado et al, 2006;Cançado et al, 2007;Santos et al, 2010;Santos et al, 2011;Leão et al, 2014;Dionísio Tavares Niewiadonski et al, 2015). The different number of samples and the region of each study can explain the variations in the frequency of the HFE gene polymorphisms in Brazil.…”

Section: Discussionmentioning

confidence: 97%

Molecular epidemiology of HFE gene polymorphic variants (C282Y, H63D and S65C) in the population of Espírito Santo, Brazil

et al. 2016

View full text Add to dashboard Cite

ABSTRACT. Hereditary hemochromatosis (HH) is an autosomal recessive disorder that leads to progressive iron accumulation and may cause cirrhosis, hepatocellular carcinoma, diabetes, and heart failure. Most cases of HH have been linked to mutations in genes associated with iron homeostasis. There have been three major variants in the high Fe (HFE) gene associated with the disease: C282Y, H63D and S65C. In this context, we aimed to evaluate the prevalence of the polymorphic variants (C282Y, H63D and S65C) of the HFE gene in the population of the Espírito Santo State (ES), Brazil by analyzing three different groups: general population (N = 120), Pomeranian descendants (N = 59), and patients with HH (N = 20). Using genomic DNA extracted from peripheral blood, polymorphic variant identification was performed by polymerase chain reaction-restriction fragment length polymorphism. Statistically significant differences were observed for genotype distribution of C282Y (P < 0.001) and H63D (P = 0.013) between the general population and the patients diagnosed with HH. This is the first study to analyze HFE gene allele frequencies for the general population, Pomeranian subpopulation, and patients with HH of ES, Brazil.

show abstract

“…It is estimated that about 500,000 Portuguese arrived in Brazil between 1500 and 1808. After the arrival of the first colonizers, the Portuguese-Amerindian-African admixture became common [6,7,8,9]. In this context, the HAMP gene mutation found in Brazilian patients could be related to our population characteristics involving Portuguese ancestry, even in patients who are not aware of their Portuguese background.…”

Section: Tablementioning

confidence: 99%