Prevalence of C282Y and H63D mutations in the HFE gene of Brazilian individuals with clinical suspicion of hereditary hemochromatosis

ABSTRACT. Development of hereditary hemochromatosis is associated with the C282Y, H63D or S65C mutations in the hemochromatosis gene. Though there is extensive knowledge about the former two, there is little information on the mechanism of action and the allelic frequency of the S65C mutation. We examined the prevalence of the S65C mutation of the hemochromatosis gene in Brazilians with clinical suspicion of hereditary hemochromatosis. Genotyping for this mutation was carried out in 633 individuals with clinical suspicion of hereditary hemochromatosis, using the polymerase chain reaction, followed by enzymatic digestion. The sample comprised 77.1% men and 22.9% women, giving a ratio of approximately 3:1; the mean age was 48.8 + 13.8 years. More than half (57.3%) of the individuals in the sample were 41 to 60 years old. The frequency of heterozygotes for this mutation was 0.016; no homozygous mutant patients were found. S65C mutation in BrazilThis is the first analysis of the S65C mutation in individuals suspected of having hereditary hemochromatosis in Brazil.

Section: Introductionmentioning

confidence: 99%

Frequency of the S65C mutation in the hemochromatosis gene in Brazil

Oliveira¹,

Caxito²,

Gomes³

et al. 2009

“…The homozygous frequencies for the C282Y mutation in both the control group and diabetic group (0%) were smaller than the frequencies observed in Caucasian (0.44%), Hispanic (0.027%) and Black (0.014%) populations (Sampson et al, 2000). For the H63D mutation, the number of homozygous and heterozygous individuals in the two groups studied (Table 1) was also smaller compared to the one reported in Brazilians with clinical suspicion of HH (Ferreira et al, 2008). No significant association could be demonstrated between the presence of the C282Y and H63D mutations and the development of DM2 in Brazilian women, in contrast to the results of other studies (Nelson et al, 1995;Kwan et al, 1998).…”

Section: Discussionmentioning

confidence: 57%

“…Few studies have been carried out in Brazil to determine the frequency of these mutations in individuals with clinical suspicion of HH. Ferreira et al (2008Ferreira et al ( ), evaluating 1955 Brazilian individuals with clinical suspicion of HH, observed that the C282Y mutation was present in homozygosity in only 2.9% and in heterozygosity in 10.1% of the subjects. The H63D mutation was found in 4.3% of the patients in homozygosity and 30.6% in heterozygosity.…”

Section: Introductionmentioning

confidence: 99%

Lack of association of C282Y and H63D mutations in the hemochromatosis (HFE) gene with diabetes mellitus type 2 in a case-control study of women in Brazil

Mg²,

Coelho³

et al. 2009

ABSTRACT.Hereditary hemochromatosis is one of the most common autosomal recessive diseases; it is characterized by excess absorption of iron. Clinically, the major challenge is to diagnose increased iron deposition before irreversible tissue damage has occurred. C282Y and H63D are the main mutations related to hereditary hemochromatosis; these mutations have been reported to be associated with increased risk of developing diabetes mellitus type 2 (DM2). We investigated whether these mutations are associated with increased risk for the development of DM2 in women in Brazil. Seventy-two women with clinical diagnosis of DM2 under treatment with hypoglycemic agents and a control group composed of 72 women with no clinical history of diabetes were studied. The C282Y and H63D mutations were determined by PCR-RFLP. Significant differences were not observed for C282Y and H63D, when we compared diabetic and non-diabetic women. We suggest that mutations C282Y and H63D in the HFE

“…Hereditary hemochromatosis (HH) is a recessive autosomal disease characterized by iron overload in the body, with a progressive accumulation of this metal in some tissues, which may lead to structural and functional damage of organs such as the heart, liver, and pancreas, as well as occasional inflammatory and oxidative processes (Ferreira et al, 2008). The clinical manifestations generally appear between 40 and 60 years of age and occur predominately in men, because the menstrual cycle and pregnancy function has a physiological control system in women (Ferreira et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…The clinical manifestations generally appear between 40 and 60 years of age and occur predominately in men, because the menstrual cycle and pregnancy function has a physiological control system in women (Ferreira et al, 2008). HH is most common among populations of Northern European ancestry.…”

Section: Introductionmentioning

confidence: 99%

Comparison of oxidative stress and the frequency of polymorphisms in the HFE gene between hemoglobin S trait blood donors and sickle cell disease patients

Viana-Baracioli¹,

Tukamoto²,

Júnior³

et al. 2011

ABSTRACT. It is well documented that Hb S and iron affect blood cells, and trigger oxidative processes and generation of free radicals with potential for lipid peroxidation. We evaluated the frequency of polymorphisms in the HFE gene in Hb AS blood donors and how these polymorphisms influenced lipid peroxidation and antioxidant capacity. Blood samples were collected from 211 Hb AS blood donors, 119 Hb AA blood donors as a control group, and 28 sickle cell disease patients (Hb SS). The H63D allele was found at a frequency of 10.5% in the Hb ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 10 (4): 3446-3454 (2011) Oxidative stress, gene HFE mutation, and HbS 3447AS samples, and the C282Y allele frequency was 0.7%. In the control group, the frequencies of the H63D and C282Y alleles were 13.4 and 2.1%, respectively. In the sickle-cell disease patients, the H63D and the C282Y allele frequencies were 10.7 and 3.5%, respectively. The frequencies of the C282Y and H63D polymorphisms in Hb AS blood donors are similar to those reported for the Brazilian population. Serum malondialdehyde values, indicative of lipid peroxidation, were highest in sickle cell patients, independent of the polymorphisms in the HFE gene, with significant differences, showing the influence of Hb S allele in the levels of lipid peroxidation. However, the trolox equivalent antioxidant capacity average levels, indicative of the antioxidant capacity, were reduced with significant differences, indicating that in spite of a lipid peroxidation raise, this is not followed by the increased of the antioxidant capacity, leading to oxidative stress.