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Progression of atherosclerosis is associated with variation in the alpha(1)-antitrypsin gene

Talmud, PJ; Martin, S; Steiner, G; Flavell, DM; Whitehouse, DB; Nagl, S; ... Diabet Atherosclerosis Interventio,; + view all (2003) Progression of atherosclerosis is associated with variation in the alpha(1)-antitrypsin gene. ARTERIOSCL THROM VAS , 23 (4) 644 - 649. 10.1161/01.ATV.0000065196.61663.8D.

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Abstract

Objective-alpha(1)-Antitrypsin (AAT) protects elastic tissue and may play a role in atherogenesis. The association of atherosclerosis progression with common AAT variants was considered in 2 clinical trials.Methods and Results - We examined the association of AAT V213A, S and Z deficiency alleles, and the functional 3' UTR 11478G>A with change in minimal luminal diameter, a measure of focal disease, in the Lopid Coronary Angiography Trial gemfibrozil study of post-bypass men. S or Z carriers (n=14) showed strong progression of disease on placebo (11.5%) but responded well to treatment (3% regression). 11478A carriers treated with placebo or gemfibrozil showed significantly more disease progression (n=8, -14.5% and n=16, -4.0%, respectively) than 11478GG men (n=107, -7.0% and n=108, -1.4%, respectively; overall, P=0.003). VV213 men treated with gemfibrozil (n=68) showed -4.8% progression, whereas A213 carriers (n=55) showed +1.4% regression of disease (P=0.001). No V213A effect was seen on placebo (P=0.11). In the Diabetes Atherosclerosis Intervention Study fenofibrate trial of angiographic progression in type 2 diabetes, the association of 11478A with increased disease progression was confirmed in the treatment group, but not the gemfibrozil-treated A213 association with regression, suggesting a pharmacogenetic difference.Conclusions-Disease progression is associated with variation in AAT, and low AAT levels promote atherogenesis.

Type:Article
Title:Progression of atherosclerosis is associated with variation in the alpha(1)-antitrypsin gene
DOI:10.1161/01.ATV.0000065196.61663.8D
Keywords:alpha(1)-antitrypsin, gene variants, atherosclerosis progression, fibrates, BASE-LINE CHARACTERISTICS, CORONARY-ARTERY DISEASE, ALPHA-1-ANTITRYPSIN DEFICIENCY, BYPASS SURGERY, INTERVENTION, MUTATION, INFLAMMATION, GEMFIBROZIL, CHOLESTEROL, SECRETION
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Structural and Molecular Biology
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

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