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Common polymorphisms of ALOX5 and ALOX5AP and risk of coronary artery disease.

TitleCommon polymorphisms of ALOX5 and ALOX5AP and risk of coronary artery disease.
Publication TypeJournal Article
Year of Publication2008
AuthorsAssimes TL, Knowles JW, Priest JR, Basu A, Volcik KA, Southwick A, Tabor HK, Hartiala J, Allayee H, Grove ML, Tabibiazar R, Sidney S, Fortmann SP, Go A, Hlatky M, Iribarren C, Boerwinkle E, Myers R, Risch N, Quertermous T
JournalHum Genet
Volume123
Issue4
Pagination399-408
Date Published2008 May
ISSN1432-1203
Keywords5-Lipoxygenase-Activating Proteins, Adolescent, Adult, African Americans, Aged, Alleles, Arachidonate 5-Lipoxygenase, Carrier Proteins, Case-Control Studies, Cohort Studies, Coronary Artery Disease, European Continental Ancestry Group, Female, Gene Frequency, Hispanic Americans, Humans, Linkage Disequilibrium, Male, Membrane Proteins, Middle Aged, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Prospective Studies, Risk Factors
Abstract

Recent human genetic studies suggest that allelic variants of leukotriene pathway genes influence the risk of clinical and subclinical atherosclerosis. We sequenced the promoter, exonic, and splice site regions of ALOX5 and ALOX5AP and then genotyped 7 SNPs in ALOX5 and 6 SNPs in ALOX5AP in 1,552 cases with clinically significant coronary artery disease (CAD) and 1,583 controls from Kaiser Permanente including a subset of participants of the coronary artery risk development in young adults study. A nominally significant association was detected between a promoter SNP in ALOX5 (rs12762303) and CAD in our subset of white/European subjects (adjusted odds ratio per minor allele, log-additive model, 1.32; P = 0.002). In this race/ethnic group, rs12762303 has a minor allele frequency of 15% and is tightly linked to variation at the SP1 variable tandem repeat promoter polymorphism. However, the association between CAD and rs12762303 could not be reproduced in the atherosclerosis risk in communities study (hazard rate ratio per minor allele; 1.08, P = 0.1). Assuming a recessive mode of inheritance, the association was not significant in either population study but our power to detect modest effects was limited. No significant associations were observed between all other SNPs and the risk of CAD. Overall, our findings do not support a link between common allelic variation in or near ALOX5 or ALOX5AP and the risk of CAD. However, additional studies are needed to exclude modest effects of promoter variation in ALOX5 on the risk of CAD assuming a recessive mode of inheritance.

DOI10.1007/s00439-008-0489-5
Alternate JournalHum Genet
PubMed ID18369664
PubMed Central IDPMC4023692
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
C06 CA62528-01 / CA / NCI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
R01 HL087647 / HL / NHLBI NIH HHS / United States
N01-HC-48047 / HC / NHLBI NIH HHS / United States
N01HC48049 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
C06 CA062528 / CA / NCI NIH HHS / United States
N01-HC-95095 / HC / NHLBI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
R01 HL087647-01 / HL / NHLBI NIH HHS / United States
N01-HC-48050 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
R01 HL079353 / HL / NHLBI NIH HHS / United States
C06 RR10600-01 / RR / NCRR NIH HHS / United States
N01HC95095 / HL / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-48049 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
N01HC48050 / HL / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
C06 RR14514-01 / RR / NCRR NIH HHS / United States
N01HC48047 / HL / NHLBI NIH HHS / United States
C06 RR014514 / RR / NCRR NIH HHS / United States
HL079353 / HL / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
N01HC48048 / HL / NHLBI NIH HHS / United States