15-lipoxygenase gene variants are associated with carotid plaque but not carotid intima-media thickness
15-lipoxygenase gene variants are associated with carotid plaque but not carotid intima-media thickness
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DOI：
10.1007/s00439-008-0496-6
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发表时间：
2008-06-01
期刊：
影响因子：
5.3
通讯作者：
Palmer, Lyle J.
中科院分区：
文献类型：
--
作者：
McCaskie, Pamela A.;Beilby, John P.;Palmer, Lyle J.
CHD 的主要根本原因是动脉粥样硬化，已知氧化的 LDL 在其发展中发挥重要作用。我们研究了 15-脂氧合酶基因 (ALOX15) 中的三个单核苷酸多态性 (SNP) 在动脉粥样硬化中的作用。我们对两个西澳大利亚样本（1,111 名社区个体和 556 名先心病患者）的 ALOX15 启动子中的 3 个 SNP 进行了基因分型。测试了 SNP 和单倍型与颈动脉斑块、内膜中层厚度和冠心病风险的关联。 -611GG 基因型与 CHD 患者颈动脉斑块可能性增加相关（OR = 4.01，95%CI = 1.39-11.53，P = 0.005），G-220C 和 G-189C SNP 的 C 等位基因与病例中颈动脉斑块可能性降低相关（OR = 0.66，95%CI = 0.43-0.99，P = 0.05 且 OR = 0.51，95%CI = 0.34-0.78，P = 0.002）。 GGG单倍型与CHD患者（OR = 5.77，95%CI = 1.82-18.29，P = 0.0007）和53岁以下社区个体（OR = 4.15，95%CI = 1.23-14.08，P = 0.02）颈动脉斑块风险增加相关。未观察到 ALOX15 SNP 或单倍型与内膜中层厚度之间存在关联。这项研究是新颖的，因为它是第一个检查 15-脂氧合酶多态性与动脉粥样硬化指标之间关联的研究。这些发现表明 ALOX15 多态性在局灶性斑块形成中可能发挥作用。
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.