Analysis of HFE And Non-HFE Gene Mutations in Brazilian Patients with Hemochromatosis

Abstract

BACKGROUNDApproximately one-half of Brazilian patients with hereditary hemochromatosis (HH) are neither homozygous for the C282Y mutation nor compound heterozygous for the H63D and C282Y mutations that are associated with HH in Caucasians. Other mutations have been described in the HFE gene as well as in genes involved in iron metabolism, such as transferrin receptor 2 (TfR2) and ferroportin 1 (SCL40A1).AIMSTo evaluate the role of HFE, TfR2 and SCL40A1 mutations in Brazilian subjects with HH.PATIENTS AND METHODSNineteen male subjects (median age 42 [range: 20–72] years) with HH were evaluated using the Haemochromatosis StripAssay A®. This assay is capable of detecting twelve HFE mutations, which are V53M, V59M, H63D, H63H, S65C, Q127H, P160delC, E168Q, E168X, W169X, C282Y and Q283, four TfR2 mutations, which are E60X, M172K, Y250X, AVAQ594-597del, and two SCL40A1 mutations, which are N144H and V162del.RESULTSIn our cohort, nine (47%) patients were homozygous for the C282Y mutation, two (11%) were heterozygous for the H63D mutation, and one each (5%) was either heterozygous for C282Y or compound heterozygous for C282Y and H63D. No other mutations in the HFE, TfR2 or SCL40A1 genes were observed in the studied patients.CONCLUSIONSOne-third of Brazilian subjects with the classical phenotype of HH do not carry HFE or other mutations that are currently associated with the disease in Caucasians. This observation suggests a role for other yet unknown mutations in the aforementioned genes or in other genes involved in iron homeostasis in the pathogenesis of HH in Brazil.

Evaluation of HFE Gene (C282Y) Mutation and Its Association Relation with Coronary Artery Diseases in Indian Population

“…The World Health Organization (WHO) estimated 20 million cardio vascular disease (CVD) deaths in 2015, accounting for 30 percent of all deaths worldwide [3][4][5]. The common autosomal recessive disorder studied in the patients of CAD is the Hereditary Hemochromatosis (HHC), which reduces iron absorption and results in excessive iron deposition in various organs of the body like the liver, pancreas, heart, joints and pituitary gland [3][4][5][6]. The age of onset of the disease varies with men and women.…”

“…It is noted generally that the disease manifests later in women. This time delay in women is due to their frequent blood loss in the form of the menstrual blood losses and pregnancies [5]. The gene associated with this disease was found out to be the HFE gene and the disease has been described with the two, missense mutations of the gene-C282Y and H63D.…”

“…The phenotypic expression of HHC is variable; it is more of interplay between the genetic factors, environmental factors, the dietary consumptions if iron, etc. [5]. Early complaints of the disease may include fatigue, weakness, joint pains, palpitations and abdominal pain.…”

“…The major endocrine disorder associated with HHC is diabetes mellitus. This is because it has been postulated that the iron deposition damages the pancreatic beta cells and provides insulin resistance [4,5]. The two allelic variants of HFE are missense mutations.…”

Hemojuvelin and Hepcidin Genes Sequencing in Brazilian Patients with Primary Iron Overload

“…The presence of lower rates of Brazilian patients carrying a homozygous genotype for the p.C282Y mutation compared with northern European patients may suggest that, in this particular population, other non-HFE mutations may be determinant in the genetic epidemiology of HH (MerryweatherClarke et al, 1997;Pereira et al, 2001;Cancado et al, 2006;Bittencourt et al, 2009).…”