Division of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan.
Hereditas. 2012 Jun;149(3):91-8. doi: 10.1111/j.1601-5223.2012.02247.x. Epub 2012 Jul 4.
CYP4A11, which is a member of the cytochrome P450 family, acts mainly as an enzyme that converts arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a metabolite involved in the maintenance of cardiovascular health. Recently, it was reported that many subfamilies of CYP genes have an association with myocardial infarction (MI). The aim of the present study was to assess the association between the human CYP4A11 gene and MI, using a haplotype-based case-control study with a separate analysis of the gender groups. A total of 239 MI patients and 285 controls were genotyped for 3 single-nucleotide polymorphisms (SNPs) of the human CYP4A11 gene (rs2269231, rs1126742, rs9333025). The data obtained via haplotype-based case-control studies were assessed for 3 separate groups: total subjects, men, and women. For the total, men and women groups, the distribution of the genotypes and alleles of the 3 SNPs did not show any significant difference between the MI patients and the control subjects. For the total and the men groups, the overall distribution of the haplotypes constructed with the 3 SNPs significantly differed between the MI patients and control subjects (P < 0.001). Also, for the total and for the men, the frequency of the T-T-A haplotype constructed with the 3 SNPs was significantly lower for the MI patients than for the control subjects (both P < 0.001). The T-T-A haplotype constructed with the 3 SNPs appears to be a protective genetic marker for MI in Japanese men.
CYP4A11 是细胞色素 P450 家族的成员，主要作为一种酶发挥作用，将花生四烯酸转化为 20-羟二十碳四烯酸（20-HETE），这是一种参与维持心血管健康的代谢物。最近，有报道称许多 CYP 基因亚家族与心肌梗死（MI）有关。本研究旨在使用基于单体型的病例对照研究，对性别组进行单独分析，评估人类 CYP4A11 基因与 MI 之间的关联。共对 239 例 MI 患者和 285 例对照进行了人类 CYP4A11 基因 3 个单核苷酸多态性（SNP）（rs2269231、rs1126742、rs9333025）的基因分型。基于单体型的病例对照研究的数据分别评估了 3 个独立组：总人群、男性和女性。对于总人群、男性和女性人群，3 个 SNP 的基因型和等位基因分布在 MI 患者和对照组之间没有显示出任何显著差异。对于总人群和男性人群，用 3 个 SNP 构建的单体型的总体分布在 MI 患者和对照组之间有显著差异（P<0.001）。此外，对于总人群和男性人群，用 3 个 SNP 构建的 T-T-A 单体型的频率在 MI 患者中明显低于对照组（均 P<0.001）。用 3 个 SNP 构建的 T-T-A 单体型似乎是日本男性 MI 的保护性遗传标志物。
