Author(s):
Barreto da Silva, Marta 
; Gaio, Vânia ; Fernandes, Aida ; Mendonça, Francisco ; Horta Correia, Filomena ; Beleza, Álvaro ; Gil, Ana Paula ; Bourbon, Mafalda ; Vicente, Astrid ; Matias Dias, Carlos
Date: 2012
Persistent ID: http://hdl.handle.net/10400.18/2122
Origin: Repositório Científico do Instituto Nacional de Saúde
Subject(s): Alpha-1 Antitrypsin Deficiency; Hereditary Hemochromatosis; Public Health Genetics; Gene Variants; Determinantes da Saúde e da Doença; Doenças Cardio e Cérebro-vasculares
Description
Alpha-1 antitrypsin (AAT) deficiency and hereditary hemochromatosis (HH) are two of the most fatal genetic disorders in adult life, affecting million individuals worldwide. They are often under-diagnosed conditions and diagnosis is only made when the patient is already in the advanced stages of damage. AAT deficiency results from mutations in one highly pleiomorphic gene located on chromosome 14, SERPINA 1, being Z and S mutations the most relevant clinically. These mutations will lead to an AAT deficit that compromises the lungs protection, originating emphysema, chronic bronchitis, asthma or even chronic obstructive pulmonary disease (COPD) and it is also strongly associated with various liver diseases. On the other hand, C282Y and H63D mutations in the HFE gene, located on chromosome 6, are reported to be mostly responsible for the iron accumulation in HH disorder, leading to severe damage in different organs. Disease manifestations include cirrhosis, hepatic fibrosis, diabetes mellitus, arthropathy and hepatocarcinoma.
Given the insufficient population-based information about the prevalence of these gene variants in the Portuguese population, the aim of this study was to assess their frequency in a representative sample from São Brás de Alportel, in the South of Portugal. To achieve our goal, we have genotyped a total of 208 adult subjects, including 118 females and 90 males (mean age: 58 years, range: 26-91). Regarding AAT deficiency, we found 4,3% MZ, 0,5% SS and 15,4% MS genotypes. The calculated frequency for the Z allele was 2,2% (95% CI: 0-11,7%) and for the S allele was 8,2% (95% CI: 0-17,4%). About HH, we found 1,4% C282Y/H63D, 2,4% H63D/H63D, 5,8% C282Y/N and 23,6% H63D/N genotypes. Frequencies of C282Y and H63D alleles were 3,6% (95% CI: 0-13%) and 14,9% (95% CI: 6-23,8%), respectively. The observed allele frequencies were in Hardy-Weinberg Equilibrium and no association was found with related diseases likely due to the smaller sample available.
Our findings show the highest prevalence of Z allele from SERPINA1 gene found, when compared to other populations. The remaining findings are in agreement with previously published studies. Future studies involving a larger sample size will be necessary to evaluate the penetrance of the studied gene mutations and to assess gene-environment interactions that influence disease risk, contributing to reduce the burden of these diseases which can have a great public health impact.
