Maznyczka, A. M., Mangino, M., Whittaker, A., Braund, P., Palmer, T., Tobin, M., Goodall, A. H., Bradding, P. and Samani, N. J. (2007) Leukotriene B4 production in healthy subjects carrying variants of the arachidonate 5-lipoxygenase-activating protein gene associated with a risk of myocardial infarction. Clinical Science, 112(7), pp. 411-416. (doi: 10.1042/CS20060271) (PMID:17176247)
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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 μmol/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.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Maznyczka, Dr Annette Marie |
Authors: | Maznyczka, A. M., Mangino, M., Whittaker, A., Braund, P., Palmer, T., Tobin, M., Goodall, A. H., Bradding, P., and Samani, N. J. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
Journal Name: | Clinical Science |
Publisher: | Portland Press |
ISSN: | 0143-5221 |
ISSN (Online): | 1470-8736 |
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