title: 15-Lipoxygenase gene variants are associated with carotid plaque but not carotid intima-media thickness.
abstract: The major underlying cause of CHD is atherosclerosis, and oxidised LDL is known to play an important role in its development. We examined the role of three single nucleotide polymorphisms (SNPs) in the 15-lipoxygenase gene (ALOX15), in atherosclerosis. We genotyped three SNPs in the ALOX15 promoter in two Western Australian samples-1,111 community-based individuals and 556 with CHD. SNPs and haplotypes were tested for an association with carotid plaque, intima-media thickness and risk of CHD. The -611GG genotype was associated with increased likelihood of carotid plaque in CHD patients (OR = 4.01, 95%CI = 1.39-11.53, P = 0.005) and the C alleles of the G-220C and G-189C SNPs were associated with decreased likelihood of plaque among cases (OR = 0.66, 95%CI = 0.43-0.99, P = 0.05 and OR = 0.51, 95%CI = 0.34-0.78, P = 0.002 respectively). The GGG haplotype was associated with increased risk of carotid plaque in CHD patients (OR = 5.77, 95%CI = 1.82-18.29, P = 0.0007) and in community-based individuals under 53 years (OR = 4.15, 95%CI = 1.23-14.08, P = 0.02). No association was observed between ALOX15 SNPs or haplotypes and intima-media thickness. This study is novel as it is the first to examine the association between 15-lipoxygenase polymorphisms and atherosclerotic indicators. These findings suggest a possible role of ALOX15 polymorphisms in focal plaque formation.
authors.affiliation: Laboratory for Genetic Epidemiology, Western Australian Institute for Medical Research, UWA Centre for Medical Research, University of Western Australia, Perth, WA, Australia. pmccask@cyllene.uwa.edu.au
authors.forename: Pamela A
authors.initials: PA
authors.lastname: McCaskie
authors.forename: John P
authors.initials: JP
authors.lastname: Beilby
authors.forename: Joseph
authors.initials: J
authors.lastname: Hung
authors.forename: Caroline M L
authors.initials: CM
authors.lastname: Chapman
authors.forename: Brendan M
authors.initials: BM
authors.lastname: McQuillan
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Powell
authors.forename: Peter L
authors.initials: PL
authors.lastname: Thompson
authors.forename: Lyle J
authors.initials: LJ
authors.lastname: Palmer
mesh_terms: D000328:Adult; D000368:Aged; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics*; D050197:Atherosclerosis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002339:Carotid Arteries / Q000033:anatomy & histology / Q000201:enzymology / Q000473:pathology*; D002340:Carotid Artery Diseases / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D017539:Tunica Intima / Q000033:anatomy & histology / Q000201:enzymology / Q000473:pathology*
chemical_list: D001093:Arachidonate 15-Lipoxygenase