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15-Lipoxygenase gene variants are associated with carotid plaque but not carotid intima-media thickness

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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.

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Acknowledgments

This study was supported by the National Heart Foundation grant-in-aid G97P 5002.

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Authors and Affiliations

  1. Laboratory for Genetic Epidemiology, Western Australian Institute for Medical Research, UWA Centre for Medical Research, University of Western Australia, Perth, WA, Australia

    Pamela A. McCaskie, Brenda L. Powell & Lyle J. Palmer

  2. School of Mathematics and Statistics, University of Western Australia, Perth, WA, Australia

    Pamela A. McCaskie

  3. Clinical Biochemistry, PathWest, Laboratory Medicine of Western Australian, Perth, WA, Australia

    John P. Beilby & Caroline M. L. Chapman

  4. School of Surgery and Pathology, University of Western Australia, Perth, WA, Australia

    John P. Beilby

  5. Sir Charles Gairdner Hospital Campus of the Heart Research Institute of Western Australia, Perth, WA, Australia

    Joseph Hung, Brendan M. McQuillan & Peter L. Thompson

  6. School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia

    Joseph Hung, Brendan M. McQuillan, Peter L. Thompson & Lyle J. Palmer

  7. Sir Charles Gairdner Hospital, Hospital Ave, B Block, Ground Floor, Nedlands, WA, 6009, Australia

    Pamela A. McCaskie

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  1. Pamela A. McCaskie
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  2. John P. Beilby
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  3. Joseph Hung
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  4. Caroline M. L. Chapman
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  8. Lyle J. Palmer
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Correspondence to Pamela A. McCaskie.

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McCaskie, P.A., Beilby, J.P., Hung, J. et al. 15-Lipoxygenase gene variants are associated with carotid plaque but not carotid intima-media thickness. Hum Genet 123, 445–453 (2008). https://doi.org/10.1007/s00439-008-0496-6

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  • DOI: https://doi.org/10.1007/s00439-008-0496-6

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