ALOX5AP

From SNPedia

The arachidonate 5-lipoxygenase-activating protein encoding gene, ALOX5AP, has been associated with inflammatory processes and also aspects of heart disease such as atherosclerosis.

A 2004 study linked haplotypes of ALOX5AP to myocardial infarction and stroke.[PMID 14770184] The main haplotypes defined are now called HapA and HapB; while the SNPs defining them are intermeshed, they appear to be exclusive (i.e. no single chromosome carries more than one of these haplotypes). The haplotypes are defined as follows:

HapA: G-T-G-A, respectively, for SNPs

• rs17222814, aka SG13S25
• rs10507391, aka SG13S114
• rs4769874, aka SG13S89
• rs9551963, aka SG13S32

HapB: A-A-A-G, respectively, for SNPs

• rs17216473, aka SG13S377
• rs10507391, aka SG13S114
• rs9315050, aka SG13S41
• rs17222842, aka SG13S35

In the original (2004) article, HapA was associated with ~2x increased risk for myocardial infarction (MI) as well as ischemic stroke in Icelandic populations (713 patients), whereas in a UK population HapB was associated with greater MI risk. Subsequent studies have presented both confirmatory and conflicting results, as follows:

• HapA shows a 1.36x higher MI risk for 450 Scottish patients [PMID 15640973]
• rs10507391 showed a 1.24x risk for stroke among males (but not females) in 639 German patients [PMID 15731479]
• Neither HapA, HapB, or any of their SNPs showed MI risk in 700 US Caucasian male patients [PMID 16778124]
• Neither HapA or HapB showed any MI risk in 3,657 German patients [PMID 17304054]
• ALOX5AP SNPs rs9579646 and rs4769874 were found to be significantly associated at both allelic (p=0.019 and p<10^-4, respectively) and genotypic levels with ischemic stroke among Caucasians but not African-Americans.[PMID 17387518]
• HapB showed a 1.67x higher MI risk in 1431 Italian patients [PMID 17505527]
• Neither HapA or HapB showed any MI risk in 685 Swedish patients [PMID 17655870]
• HapB showed a higher MI risk among 1,211 German patients [PMID 18318662]
• No ALOX5AP SNPs were found to be linked to coronary artery disease in a study of 1500 patients [PMID 18369664]

Additionally, while some studies have shown that treatment with a leukotriene inhibitor reduces biomarkers of coronary risk in patients carrying HapA, others have concluded that knowledge of a patient's ALOX5AP haplotype may not provide useful information on the probable clinical response to ALOX5AP inhibitors.[PMID 17176247]