Genetic risk factors for ischemic cerebrovascular disease - studies of 15 candidate prothrombotic gene polymorphisms in the japanese population

Keiko Ishii, Shuji Oguchi, Daisuke Ito, Norio Tanahashi, Yasuo Fukuuchi, Ikuo Saito, Eiko Takeshita, Mitsuru Murata, Yasuo Ikeda, Kiyoaki Watanabe

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Accumulating evidence suggests that several polymorphisms in factors regulating blood coagulation, platelet function, and lipid metabolism are relevant for susceptibility to ischémie cerebrovascular diseases (CVD). Allele frequencies of common polymorphisms, however, are different among races; i.e., the factor V Leiden and the prothrombin 20210A mutations are absent or very rare in Orientals. This study analyzed 15 genetic polymorphisms possibly relevant for atherosclerosis and thrombosis in a case-control study involving 200 genetically unrelated Japanese patients with ischémie CVD (mean age 58.3 ±7.6 y) and 281 age- and gender-matched control subjects (59.0 ±4.1 y). CVD was confirmed by brain CT and/or MRI, and was classified as atherothrombotic infarction (n=52), lacunar infarction (n=126), and transient ischémie attack (n=22), based on the classification of cerebrovascular diseases III established by the National Institute of Neurological Disorders and Stroke. Control subjects were unrelated donors with no history of documented CVD or any type of cardiovascular disease. The polymorphisms analyzed were methylenetetrahydrofolate reductase (C677T), paraoxonase (Glnl92Arg). apolipoprotein E (e2, s3, £4), cholesteryl ester transfer protein (Taq IB, intron 1), angiotensin-converting enzyme (insertion/deletion), nitric-oxide synthase (4 repeat/5 repeat), 5HT2A receptor (T102C), platelet glycoprotein (GP) Iba (Thrl45Met), fibrinogen (-chain, G-455A), coagulation factor XII (C46T), PAI-1 (promoter 4G/5G), NADPH oxidase p22 phox (His72Tyr), mitochondria! DNA (C5178A), monocyte CD14 (promoter C-260T), and atrial natriuretic peptide (G664A). Among the factors genotyped, two factors, GPIbtx (Thrl45Met) and NADPH oxidase p22 phox (His72Tyr), were significantly associated with CVD after adjustment for acquired risk factors including hypertension, diabetes mellitus, hyperlipidemia, and smoking. For those with age < 60 y, 10.6% of the CVD patients and 2.9% of the control subjects had both of the two risk genotypes (GPIba 145Met and p22 phox 72Tyr, p<0.05). The mean onset-age of CVD was 58.6 ±7.7 y for those having no or only one risk genotype, and 53.3 ±5.5 y for those with both of the risk genotypes (p<0.05). Thus, GPIba 145Met and p22 phox 72Tyr are the genetic factors associated with ischémie CVD in the Japanese. Carrying both of the two mutations might be associated with developing CVD at a younger age.

元の言語English
ページ(範囲)97b
ジャーナルBlood
96
発行部数11 PART II
出版物ステータスPublished - 2000 12 1

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Ishii, K., Oguchi, S., Ito, D., Tanahashi, N., Fukuuchi, Y., Saito, I., Takeshita, E., Murata, M., Ikeda, Y., & Watanabe, K. (2000). Genetic risk factors for ischemic cerebrovascular disease - studies of 15 candidate prothrombotic gene polymorphisms in the japanese population. Blood, 96(11 PART II), 97b.