Summary
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). The respective mean values among Japanese were 251 mg/dl for B1B1 and 257 mg/dl
for B1B2 or B2B2 combined (p = 0.37), 248 mg/dl for Hd1Hd1 and 259 mg/dl for Hd1Hd2
or Hd2Hd2 combined (p = 0.16). These polymorphisms had a similar effect on plasma
fibrinogen concentrations for both men and women. The results suggest that a genetic
difference may partly explain the higher plasma fibrinogen in Caucasians than in Japanese.
