Nishiuma S, Kario K, Yakushijin K, Maeda M, Murai R, Matsuo T, Ikeda U, Shimada K, Matsuo M
Division of Genetics, International Center for Medical Research, Kobe University School of Medicine, Japan.
Blood Coagul Fibrinolysis. 1998 Jun;9(4):373-9. doi: 10.1097/00001721-199806000-00010.
Evidence suggests that an allelic variation in the beta fibrinogen gene may confer an increased risk of coronary artery disease and stroke. The role of the beta fibrinogen gene polymorphism and fibrinogen levels in ischemic stroke has not been determined in Japanese, who are more prone to stroke than to coronary artery disease compared with Caucasians. We investigated the associations between ischemic stroke, plasma fibrinogen level, and a HaeIII restriction fragment length polymorphism (G/A(-455)) located at -455 bp from the start of transcription of the beta fibrinogen gene in 85 hypertensive patients with ischemic stroke (stroke group), 85 hypertensive patients without ischemic stroke (nonstroke group) and in 84 normotensive subjects matched for age, sex, and smoking status recruited at an annual health examination (normotensive group). The frequency of non-cutting allele (designated A(-455) allele) in the control group was 0.07 [95% CI: 0.03-0.11]; this value was significantly lower than that previously reported in Caucasians (0.19-0.26). The A(-455) allele frequency of the nonstroke group and stroke group were 0.08 [95% CI: 0.04-0.12] and 0.15 [95% CI: 0.10-0.21]. A(-455) allele frequency of the stroke group was significantly higher than that of the control group chi2 = 5.63, P= 0.018) and the nonstroke group chi2 = 4.00, P= 0.043). The mean +/- SD fibrinogen level was significantly higher in the stroke group than that in the normotensive group (277 +9/- 64 mg/dl versus 257 +/- 52 mg/dl, P < 0.03), but that of the nonstroke group was not significantly different compared with both normotensive and stroke groups. In conclusion, the positive association between the fibrinogen genotype G/A(-455) and ischemic stroke in hypertensive patients was independent of other risk factors. These results suggest that fibrinogen A(-455) allele may be an independent risk factor for ischemic stroke in the Japanese population.
有证据表明，β纤维蛋白原基因的等位基因变异可能会增加患冠状动脉疾病和中风的风险。与白种人相比，日本人更容易患中风而非冠状动脉疾病，然而β纤维蛋白原基因多态性和纤维蛋白原水平在日本缺血性中风患者中的作用尚未明确。我们调查了85例患有缺血性中风的高血压患者（中风组）、85例未患缺血性中风的高血压患者（非中风组）以及84例在年度健康检查中招募的年龄、性别和吸烟状况相匹配的血压正常受试者（血压正常组），研究缺血性中风、血浆纤维蛋白原水平与位于β纤维蛋白原基因转录起始点-455 bp处的HaeIII限制性片段长度多态性（G/A(-455)）之间的关联。对照组中未切割等位基因（称为A(-455)等位基因）的频率为0.07 [95%置信区间：0.03 - 0.11]；该值显著低于先前报道的白种人频率（0.19 - 0.26）。非中风组和中风组的A(-455)等位基因频率分别为0.08 [95%置信区间：0.04 - 0.12]和0.15 [95%置信区间：0.10 - 0.21]。中风组的A(-455)等位基因频率显著高于对照组（χ2 = 5.63，P = 0.018）和非中风组（χ2 = 4.00，P = 0.043）。中风组的平均±标准差纤维蛋白原水平显著高于血压正常组（277 ± 9/- 64 mg/dl对257 ± 52 mg/dl，P < 0.03），但非中风组与血压正常组和中风组相比无显著差异。总之，纤维蛋白原基因型G/A(-455)与高血压患者缺血性中风之间的正相关独立于其他危险因素。这些结果表明，纤维蛋白原A(-455)等位基因可能是日本人群缺血性中风的独立危险因素。
