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Alpha-1 antitrypsin deficiency: From the lung to the heart?

Curjuric, Ivan and Imboden, Medea and Bettschart, Robert and Caviezel, Seraina and Dratva, Julia and Pons, Marco and Rothe, Thomas and Schmidt-Trucksäss, Arno and Stolz, Daiana and Thun, Gian Andri and von Eckardstein, Arnold and Kronenberg, Florian and Ferrarotti, Ilaria and Probst-Hensch, Nicole M.. (2018) Alpha-1 antitrypsin deficiency: From the lung to the heart? Atherosclerosis, 270. pp. 166-172.

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Official URL: https://edoc.unibas.ch/60961/

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Abstract

BACKGROUND AND AIMS:
Alpha-1 antitrypsin (A1AT) is the most abundant serine protease inhibitor in human blood and exerts important anti-inflammatory and immune-modulatory effects. In combination with smoking or other long-term noxious exposures such as occupational dust and fumes, genetic A1AT deficiency can cause chronic obstructive pulmonary disease, a condition with elevated cardiovascular risk. The effects of A1AT deficiency on cardiovascular risk have hardly been studied today.
METHODS:
Using data from 2614 adults from the population-based SAPALDIA cohort, we tested associations of serum A1AT and SERPINA1 mutations with carotid intima-media thickness (CIMT, measured by B-mode ultrasonography) or self-reported arterial hypertension or cardiovascular disease in multiple regression models using a Mendelian Randomization like analysis design. Mutations Pi-S and Pi-Z were coded as ordinal genotype score (MM, MS, MZ/SS, SZ and ZZ), according to their progressive biological impact.
RESULTS:
Serum A1AT concentration presented a u-shaped association with CIMT. At the lower end of the A1AT distribution, an analogous, linear association between SERPINA1 score and higher CIMT was observed, resulting in an estimated 1.2% (95%-confidence interval -0.1-2.5) increase in CIMT per unit (p = 0.060). Genotype score was significantly associated with arterial hypertension with an odds ratio (OR) of 1.2 (1.0-1.5) per unit (p = 0.028). The association with cardiovascular disease was not significant (OR 1.3 (0.9-1.9)).
CONCLUSIONS:
Our results support a possible causal relationship between genetic A1AT deficiency and increased cardiovascular risk, which needs to be better taken into account for the management of affected patients and first-degree relatives.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
UniBasel Contributors:Curjuric, Ivan and Imboden, Medea and Dratva, Julia and Thun, Gian Andri and Probst-Hensch, Nicole
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1567-5688
e-ISSN:1878-5050
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:21 Mar 2018 13:22
Deposited On:21 Mar 2018 13:22

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