Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/7339
Title: Leukotriene B4 production in healthy subjects carrying variants of the arachidonate 5-lipoxygenase-activating protein gene associated with a risk of myocardial infarction
Authors: Maznyczka, Annette
Mangino, Massimo
Whittaker, Andrew
Braund, Peter S.
Palmer, Thomas M.
Tobin, Martin D.
Goodall, Alison H.
Bradding, Peter
Samani, Nilesh J.
First Published: Apr-2007
Publisher: Portland Press
Citation: Clinical Science, 2007, 112 (7), pp. 411-416.
Abstract: Leukotrienes are implicated in the pathogenesis of coronary artery disease. Recently two haplotypes (HapA and HapB) in the gene encoding ALOX5AP (arachidonate 5-lipoxygenase-activating protein), the main regulator of 5-lipoxygenase, have been associated with a doubling of the risk of myocardial infarction. Studies have also shown that treatment with a leukotriene inhibitor reduces biomarkers of coronary risk in patients carrying HapA, raising the possibility of developing genotype-specific therapy. In the present study, we examined whether carriage of HapA or HapB is associated with increased LTB4 (leukotriene B4) production in healthy subjects. Age- and gender-matched healthy HapA carriers (n=21), HapB carriers (n=20) and non-A/non-B carriers (n=18), with no reported history of cardiovascular disease, were recruited following DNA screening of 1268 subjects from a population-based study. Blood neutrophils were isolated, and LTB4 production was measured in response to stimulation with 1 mmol/l of the calcium ionophore A23187. There was no difference in the mean level for LTB4 production in the three groups (non-A/non-B, 24.9±8.3 ng/106 cells; HapA, 22.2±11.9 ng/106 cells; HapB, 19.8±4.8 ng/106; P=0.14). The findings indicate that if either the HapA or the HapB haplotype of ALOX5AP indeed increases cardiovascular risk, then the mechanism is not simply due to a systematically observable effect of the haplotype on LTB4 production in response to stimulation. The results suggest that knowledge of a patient's haplotype may not provide useful information on the probable clinical response to ALOX5AP inhibitors.
ISSN: 0143-5221
Links: http://dx.doi.org/10.1042/CS20060271
http://hdl.handle.net/2381/7339
Type: Article
Description: This paper was published as Clinical Science, 2007, 112 (7), pp. 411-416. It is available from http://www.clinsci.org/cs/112/cs1120411.htm. Doi: 10.1042/CS20060271
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Appears in Collections:Published Articles, Dept. of Health Sciences

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