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Association of polymorphisms in the ALOX15B gene with coronary artery disease


Wuest, Sophia J A; Horn, Thomas; Marti-Jaun, Jacqueline; Kühn, Hartmut; Hersberger, Martin (2014). Association of polymorphisms in the ALOX15B gene with coronary artery disease. Clinical Biochemistry, 47(6):349-355.

Abstract

BACKGROUND: Atherosclerosis is a multifactorial disease and the underlying cause of coronary artery disease (CAD), myocardial infarction and stroke. Two main features are involved in the progression of atherosclerosis, lipid retention and inflammation. 12/15-lipoxygenases are involved in inflammation and have been implicated in atherosclerosis. Genetic association studies of the 15-lipoxygenase 1 (ALOX15) in humans revealed a neutral to atheroprotective role of the enzyme. Recently the epidermis-type 15-lipoxygenase 2 (ALOX15B) has been identified in human atherosclerotic plaques but its role in human atherosclerosis is still unclear.
METHODS: We screened the ALOX15B gene for polymorphisms and investigated the association of 18 detected polymorphisms with angiographically documented CAD in a case-control study (n=496). In addition, we measured in vitro the enzyme activity and Michaelis-Menten kinetics of the detected non-synonymous polymorphic variants p.Arg486His (c.1457G>A), p.Gln656Arg (c.1967A>G) and p.Ile676Val (c.2026A>G).
RESULTS: We found that the linked polymorphisms at position c.1458-38G>C, c.1579+71C>T and c.1656G>A are associated with CAD (OR: 0.51 (0.27-0.94), p-value: 0.03). In addition, we show that the activity and the kinetics of the three non-synonymous ALOX15B enzyme variants (p.Arg486His, p.Gln656Arg and p.Ile676Val) are similar to the wild-type enzyme.
CONCLUSIONS: Our data indicate that the ALOX15B gene may be associated with coronary artery disease. However, larger studies would be necessary to confirm the association of these polymorphisms with CAD. In contrast, our study did not find frequent non-synonymous polymorphisms in ALOX15B altering enzyme activity in Europeans.

Abstract

BACKGROUND: Atherosclerosis is a multifactorial disease and the underlying cause of coronary artery disease (CAD), myocardial infarction and stroke. Two main features are involved in the progression of atherosclerosis, lipid retention and inflammation. 12/15-lipoxygenases are involved in inflammation and have been implicated in atherosclerosis. Genetic association studies of the 15-lipoxygenase 1 (ALOX15) in humans revealed a neutral to atheroprotective role of the enzyme. Recently the epidermis-type 15-lipoxygenase 2 (ALOX15B) has been identified in human atherosclerotic plaques but its role in human atherosclerosis is still unclear.
METHODS: We screened the ALOX15B gene for polymorphisms and investigated the association of 18 detected polymorphisms with angiographically documented CAD in a case-control study (n=496). In addition, we measured in vitro the enzyme activity and Michaelis-Menten kinetics of the detected non-synonymous polymorphic variants p.Arg486His (c.1457G>A), p.Gln656Arg (c.1967A>G) and p.Ile676Val (c.2026A>G).
RESULTS: We found that the linked polymorphisms at position c.1458-38G>C, c.1579+71C>T and c.1656G>A are associated with CAD (OR: 0.51 (0.27-0.94), p-value: 0.03). In addition, we show that the activity and the kinetics of the three non-synonymous ALOX15B enzyme variants (p.Arg486His, p.Gln656Arg and p.Ile676Val) are similar to the wild-type enzyme.
CONCLUSIONS: Our data indicate that the ALOX15B gene may be associated with coronary artery disease. However, larger studies would be necessary to confirm the association of these polymorphisms with CAD. In contrast, our study did not find frequent non-synonymous polymorphisms in ALOX15B altering enzyme activity in Europeans.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2014
Deposited On:31 Mar 2014 15:48
Last Modified:05 Apr 2016 17:48
Publisher:Elsevier
ISSN:0009-9120
Publisher DOI:https://doi.org/10.1016/j.clinbiochem.2013.12.013
PubMed ID:24373925

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