Iso H, Folsom A R, Winkelmann J C, Koike K, Harada S, Greenberg B, Sato S, Shimamoto T, Iida M, Komachi Y
Institute of Community Medicine, University of Tsukuba, Japan.
Thromb Haemost. 1995 Jan;73(1):106-11.
We reported previously that plasma fibrinogen was significantly higher in U.S. Caucasians than in Japanese, which may contribute to the higher mortality rate of coronary heart disease in the United States than in Japan. To examine the contribution of genetic variations to the race difference in plasma fibrinogen levels, restriction fragment length polymorphisms (RFLPs) of the beta fibrinogen gene were examined in 293 nonsmoking Caucasians and Japanese men and women aged 47-69 years. Three RFLPs were detected by digestion of genomic DNA using the BclI restriction enzyme, polymerase chain reaction (PCR) products using HaeIII and HindIII. The alleles B2 (4.2 kb, BclI digestion), H2 (957 b, HaeIII) and Hd2 (465 b. HindIII) were associated with higher fibrinogen concentrations in previous studies. Because of a strong linkage disequilibrium between HaeIII and HindIII polymorphisms, the data of HindIII was presented. The frequency of the B2 allele was 22% (95% Cl: 17-27%) for Caucasians and 13% (10-17%) for Japanese (the difference: p < 0.01). The respective frequency of the Hd2 allele was 26% (21-31%) and 12% (8-16%) (p < 0.001). After controlling for age, body mass index, alcohol intake, triglycerides, fish intake, and for women, menopausal status and hormone replacement therapy, the adjusted mean fibrinogen level among Caucasians was 289 mg/dl for genotype B1B1 and 301 mg/dl for genotype B1B2 or B2B2 combined (p = 0.18), and 285 mg/dl for Hd1Hd1 and 306 mg/dl for Hd1Hd2 or Hd2Hd2 combined (p = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
我们之前报道过，美国白种人的血浆纤维蛋白原水平显著高于日本人，这可能是美国冠心病死亡率高于日本的原因之一。为了研究基因变异对血浆纤维蛋白原水平种族差异的影响，我们检测了293名年龄在47至69岁之间的非吸烟白种人和日本男性及女性的β纤维蛋白原基因限制性片段长度多态性（RFLP）。使用BclI限制性内切酶消化基因组DNA、HaeIII和HindIII消化聚合酶链反应（PCR）产物，检测到三种RFLP。在之前的研究中，等位基因B2（4.2 kb，BclI消化）、H2（957 b，HaeIII）和Hd2（465 b，HindIII）与较高的纤维蛋白原浓度相关。由于HaeIII和HindIII多态性之间存在强连锁不平衡，因此展示了HindIII的数据。白种人中B2等位基因的频率为22%（95%可信区间：17 - 27%），日本人为13%（10 - 17%）（差异：p < 0.01）。Hd2等位基因的相应频率分别为26%（21 - 31%）和12%（8 - 16%）（p < 0.001）。在控制了年龄、体重指数、酒精摄入量、甘油三酯、鱼类摄入量后，对于女性还控制了绝经状态和激素替代疗法，白种人中基因型B1B1的调整后平均纤维蛋白原水平为289 mg/dl，基因型B1B2或B2B2合并的为301 mg/dl（p = 0.18），Hd1Hd1为285 mg/dl，Hd1Hd2或Hd2Hd2合并的为306 mg/dl（p = 0.03）。（摘要截断于250字）
