Human leucocyte antigens class II allele and haplotype association with Type 1 Diabetes in Madeira Island (Portugal).

This study confirms for Madeira Island (Portugal) population the Type 1 Diabetes (T1D) susceptible and protective Human leucocyte antigens (HLA) markers previously reported in other populations and adds some local specificities. Among the strongest T1D HLA associations, stands out, as susceptible, the alleles DRB1*04:05 (OR = 7.3), DQB1*03:02 (OR = 6.1) and DQA1*03:03 (OR = 4.5), as well as the haplotypes DRB1*04:05-DQA1*03:03-DQB1*03:02 (OR = 100.9) and DRB1*04:04-DQA1*03:01-DQB1*03:02 (OR = 22.1), and DQB1*06:02 (OR = 0.07) and DRB1*15:01-DQA1*01:02-DQB1*06:02 (OR = 0.04) as protective. HLA-DQA1 positive for Arginine at position 52 (Arg52) (OR = 15.2) and HLA-DQB1 negative for Aspartic acid at the position 57 (Asp57) (OR = 9.0) alleles appear to be important genetic markers for T1D susceptibility, with higher odds ratio values than any single allele and than most of the haplotypes. Genotypes generated by the association of markers Arg52 DQA1 positive and Asp57 DQB1 negative increase T1D susceptibility much more than one would expected by a simple additive effect of those markers separately (OR = 26.9). This study also confirms an increased risk for DRB1*04/DRB1*03 heterozygote genotypes (OR = 16.8) and also a DRB1*04-DQA1*03:01-DQB1*03:02 haplotype susceptibility dependent on the DRB1*04 allele (DRB1*04:01, OR = 7.9; DRB1*04:02, OR = 3.2; DRB1*04:04, OR = 22.1).

HLA-DQA1 and HLA-DQB1 allele diversity and its extended haplotypes in Madeira Island (Portugal).

This study shows, for the first time, high-resolution allele frequencies of HLA-DQA1 loci in Madeira Island (Portugal) and allows us to better understand and refine present knowledge on DQB1 variation, with the identification of several alleles not previously reported in this population. Estimates on haplotype profile, involving HLA-A, HLA-B, HLA-DRB1, HLA-DQA1 and HLA-DQB1, are also reported.

[HLA-B27 polymorphism and spondyloarthropathies]. / Polimorfismo do alelo HLA-B27 no desenvolvimento das espondilartropatias.

The association of HLA-B27 with ankylosing spondylitis (AS), and other spondyloarthropathies (SpA), remains as one of the strongest between HLA molecules and human disease. Since it was reported, in 1973, it has been extensively studied in order to understand the underlying pathogenic mechanism. The objective of this article is to review the current knowledge on the structure and polymorphism of HLA-B27 molecule, as well as describe the main pathogenic hypotheses trying to explain its association with AS.

HLA class I variation in the West African Pygmies and their genetic relationship with other African populations.

We have studied the polymorphism of HLA class I in two West African Pygmy populations, namely, the Bakola from Cameroon and the Mbenzele from the Central African Republic. A unique number of HLA alleles and haplotypes showed specific patterns of these populations. In this study, we identify two alleles (B*37, B*41) and three haplotypes (A*30-B*37, A*66-B*41 and A*68-B*58) that appear to be 'private' or typical of Western Pygmies. These data reflect similarities with the AKA Pygmies from the Central African Republic. On the other hand, we failed to identify alleles that are found at high frequencies among other sub-Saharan populations (B*42, B*51). Allelic and haplotypic frequency distributions show differences between the two Pygmy groups, e.g. B*35 was very common in the Mbenzele but has been found to be absent in the Bakola. In contrast, B*53, which is found in the Bakola, has been found to be rare in the Mbenzele Pygmies. In order to analyse the genetic relationships of the Bakola and Mbenzele Pygmies with other sub-Saharan populations, HLA gene frequencies were subjected to the Neighbour-Joining tree analysis. The Mbenzele, Bakola and AKA were found to be relatively close to each other and isolated from other sub-African populations. However, both the genetic distances and the within-group variation suggests that the Bakola are more admixed with Bantu farmers than Mbenzele.

Airway flow limitation in patients with vibroacoustic disease.

INTRODUCTION: Vibroacoustic disease (VAD) is a pathology caused by occupational exposure to large pressure amplitude and low frequency (LPALF) noise (> or =90 dB SPL, < or =500 Hz), and has been the object of study by this group for the past 20 yr. In a group of 140 VAD-diagnosed patients, 7 non-smoker aircraft technicians developed clinical signs of respiratory insufficiency at an early age. Previously, multi-focal fibrosis had been observed in the lung of Wistar rats exposed to occupationally simulated LPALF noise and with no possibility of contamination by fumes, dust or other chemical agents. The goal of this study is to compare pulmonary imaging and/or functional changes in two age- and exposure-time matched groups of VAD-diagnosed aircraft technicians, with and without airflow limitation symptoms. METHODS: In a population of 140 individuals occupationally exposed to LPALF noise and diagnosed with VAD, we excluded the smokers (45 cases) and selected 7 individuals with complaints of airway flow limitations, average age 42.3 yr (SD = 2.3). From the remaining non-smokers without respiratory complaints, we selected a group of 15, age-matched patients (average age 36 yr, SD = 6.5). All subjects received a high-resolution CT scan of the chest and respiratory function tests consisting of body plethysmography, spirometry and metacholine airway provocation. RESULTS: There is a significant relationship between the presence of symptoms and imaging of lung fibrosis through high-resolution CT scan (p = 0.03624). There are no significant differences when both groups are compared with respect to the percentage of predicted values of lung function: Vital Capacity (VC), Total Lung Capacity, Forced Expiratory Volume during the first second of expiration, Maximal Expiratory Flow at 50% VC, Total Airway Resistance, and Airway Reactivity after 25 mg of metacholine. CONCLUSION: High resolution CT scan is a valuable tool for diagnosis of lung fibrosis in VAD patients who have symptoms of airway flow limitations. The fact that lung ventilation tests did not present significant changes between both groups is in agreement with findings in Wistar rats. This strongly suggests that a process of focal pulmonary fibrosis may be induced by occupational noise exposure, and is a feature of VAD.