Effects of a 5-Lipoxygenase–Activating Protein Inhibitor on Biomarkers Associated With Risk of Myocardial Infarction

Sex-Specific Association of Depression and a Haplotype in Leukotriene A4 Hydrolase Gene

“…Common genetic vulnerability has been proposed as an explanation for the comorbidity between these two disorders (3,50). Our finding of an association between HapE and depression, taken together with the reported associations between other leukotriene haplotypes (HapA, B, and K) and cardiovascular diseases (26,27,51,52), suggests that the leukotriene metabolic pathway is a likely candidate in the search for a common genetic mechanism linking depression and cardiovascular disease. This result may explain why both depression and cardiovascular disease have been linked to an increased inflammatory response.…”

Correction to Leukotriene Receptors

“…5,6 Interestingly, DG-031 reduced the levels of biomarkers, serum C-reactive protein and amyloid-A, in MI patients with specific at-risk variants in either FLAP or LTA 4 hydrolase gene. 7 data further support the implication of 5-LO in the ment of this disease. 8,9 Various LT receptors are expressed in HUVECs, macrophages, smooth muscle, and activated T-cells.…”

Leukotriene B4 production in healthy subjects carrying variants of the arachidonate 5-lipoxygenase-activating protein gene associated with a risk of myocardial infarction

“…They indicate that if either the HapA or HapB haplotype of ALOX5AP genuinely increase cardiovascular risk, then the mechanism is not simply due to a systematically observable effect of the haplotype on LTB 4 production in response to stimulation. The other important implication of our present finding is in relation to the use of ALOX5AP inhibitors as therapeutic targets for treating atherosclerotic diseases [5,22]. Although the study by Hakonarson et al [22] showed that treatment with DG-031 reduced biomarkers of cardiovascular risk in subjects carrying HapA, our results raise the question as to whether the effect is quantitatively or qualitatively genotype-specific or likely to be observed to a similar degree in all subjects.…”

“…The other important implication of our present finding is in relation to the use of ALOX5AP inhibitors as therapeutic targets for treating atherosclerotic diseases [5,22]. Although the study by Hakonarson et al [22] showed that treatment with DG-031 reduced biomarkers of cardiovascular risk in subjects carrying HapA, our results raise the question as to whether the effect is quantitatively or qualitatively genotype-specific or likely to be observed to a similar degree in all subjects. This could have important bearing on the future clinical utility of this class of drugs and the design of outcome trials.…”