Phenotypic differences in alpha 1 antitrypsin-deficient sibling pairs may relate to genetic variation

Wood, Alice M., Needham, Michelle, Simmonds, Matthew J. , Newby, Paul R., Gough, Stephen C. and Stockley, Robert A. (2009) Phenotypic differences in alpha 1 antitrypsin-deficient sibling pairs may relate to genetic variation. COPD: Journal of Chronic Obstructive Pulmonary Disease, 5 (6). pp. 353-359. ISSN 1541-2555

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Alpha-1-antitrypsin deficiency is associated with variable development of airflow obstruction and emphysema. Index patients have greater airflow obstruction than subjects detected by screening, but it is unclear if this reflects smoking differences and/or ascertainment bias, or is due to additional genetic factors. In this study 72 sibling pairs with alpha-1-antitrypsin deficiency were compared using lung function measurements and HRCT chest. Tag single nucleotide polymorphisms to cover all common variation in four genes involved in relevant inflammatory pathways (Tumour necrosis factor alpha, Transforming growth Factor beta, Surfactant protein B and Vitamin D binding protein) were genotyped using TaqMan® technology and compared between pairs for their frequency and relationship to lung function. 63.5 of non-index siblings had airflow obstruction and 59.5 an FEV1 < 80 predicted. Index siblings had lower FEV1 and FEV1/FVC ratio, a higher incidence of emphysema (all P � 0.001) and lower gas transfer (P = 0.02). There was no correlation of FEV1 between siblings but KCO was significantly correlated (r = 0.42, P = 0.002). Quantitative analyses against lung function showed that a polymorphism in Surfactant protein B was associated with FEV1 (P = 0.002). This result was replicated in a non-sibling group (P = 0.01). Our results show that clinical differences in families with alpha-1-antitrypsin deficiency are not solely explained by smoking or ascertainment bias and may be due to variation within genes involved in inflammatory pathways. © 2008 Informa UK Ltd All rights reserved.

Keywords:surfactant protein B, transforming growth factor beta, vitamin D binding protein, alpha 1 antitrypsin deficiency, article, chronic obstructive lung disease, forced expiratory volume, genetic variability, genetics, human, lung emphysema, pathophysiology, phenotype, single nucleotide polymorphism, vital capacity, alpha 1-Antitrypsin Deficiency, Genetic Variation, Humans, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Pulmonary Surfactant-Associated Protein B, Vital Capacity, Vitamin D-Binding Protein
Subjects:C Biological Sciences > C431 Medical Genetics
Divisions:College of Science > School of Life Sciences
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ID Code:22617
Deposited On:01 Apr 2016 09:55

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