Pi*S and Pi*Z alpha 1 antitrypsin polymorphism and the risk for asbestosis in occupational exposure to asbestos

Novel Resequencing Chip Customized to Diagnose Mutations in Patients With Inherited Syndromes of Intrahepatic Cholestasis

“…In addition, we chose to add SERPINA1 to the chip as an investigative tool for studies examining how α1AT polymorphisms may serve as disease modifiers in subjects harboring mutations in one of the other cholestatic genes, or in subjects with other forms of liver disease in a fashion described for patients with chronic pulmonary diseases. [40][41][42] In summary, we customized a state-of-the-art resequencing technology to read a comprehensive nucleotide sequence of the five genes responsible for the most common forms of inherited cholestasis. The combined large size of these genes and the lack of hot spots for disease-causing mutations make it time-consuming and costly to use genetic testing by standard sequencing methodologies in the evaluation of patients with cholestasis.…”

1-Antitrypsin deficiency and lung disease: risk modification by occupational and environmental inhalants

“…8 (1.1-30.3) for PiMZ and 5.0 (1.4-17.7) for AAT level f35 mmol?L -1 ) [38]. PiZ heterozygosity or PiSS was significantly more prevalent in asbestosis cases compared with control workers with a similar asbestos exposure (8.0 (1.6-39.1)) [40].…”

“…[39] and FEV1 f65% predicted [26]. Two publications investigated the impact of AAT deficiency on highly specific occupational disorders, such as byssinosis [38] and asbestosis [40]. Investigated environmental and occupational modifiers of an AAT effect were primarily related to occupational exposures (gas, fumes, dusts, endotoxin, asbestos) [26,27,[29][30][31][32][34][35][36][37][38][39][40], with a few studies investigating exposure to passive smoking and industry and traffic-related air pollution [26,28,29,33,[41][42][43].…”

“…Investigated environmental and occupational modifiers of an AAT effect were primarily related to occupational exposures (gas, fumes, dusts, endotoxin, asbestos) [26,27,[29][30][31][32][34][35][36][37][38][39][40], with a few studies investigating exposure to passive smoking and industry and traffic-related air pollution [26,28,29,33,[41][42][43]. The combined effect of AAT deficiency and environmental exposures on lung health has been investigated predominantly in cross-sectional studies, except for one case-control study [40], and two studies reporting longitudinal data [37,43]. Five studies investigated occupational risks and passive smoking exposure in persons with severe AAT deficiency.…”

“…Intermediate AAT deficiency was also related to the risk of typical occupational diseases, namely endotoxin-related byssinosis and asbestosis [38,40]. After adjusting for potential confounders, the PiMZ phenotype or a serum AAT level ,35 mmol?L -1 were related to a significant increased odds ratio (OR (95% confidence interval (CI))) for byssinosis (5.…”