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Polymorphisms of the beta fibrinogen gene and plasma fibrinogen concentration in Caucasian and Japanese population
H Iso1, A R Folsom, J C Winkelmann
1Institute of Community Medicine, University of Tsukuba, Japan.
Insights
Genetic variations in the beta fibrinogen gene may explain higher plasma fibrinogen levels in Caucasians compared to Japanese individuals. These differences could influence coronary heart disease risk between populations.
Area of Science:
- Genetics
- Cardiovascular Disease Epidemiology
- Biochemistry
Background:
- Plasma fibrinogen levels are higher in U.S. Caucasians than Japanese, potentially contributing to increased coronary heart disease (CHD) mortality in the U.S.
- Genetic factors may underlie racial differences in plasma fibrinogen concentrations.
Purpose of the Study:
- To investigate the association between genetic variations in the beta fibrinogen gene and plasma fibrinogen levels in Caucasians and Japanese individuals.
- To determine if specific restriction fragment length polymorphisms (RFLPs) of the beta fibrinogen gene contribute to observed racial differences in fibrinogen levels.
Main Methods:
- Examined three RFLPs (BclI, HaeIII, HindIII) in the beta fibrinogen gene of 293 non-smoking Caucasian and Japanese adults (aged 47-69).
- Analyzed allele frequencies and their association with plasma fibrinogen levels, controlling for covariates like age, BMI, and lifestyle factors.
- Utilized polymerase chain reaction (PCR) and restriction enzyme digestion for RFLP detection.
Main Results:
- The B2 allele (BclI) and Hd2 allele (HindIII) were more frequent in Caucasians than Japanese (p < 0.01 and p < 0.001, respectively).
- The Hd2 allele was significantly associated with higher adjusted mean fibrinogen levels (p = 0.03).
- The B2 allele showed a trend towards association with higher fibrinogen levels in Caucasians (p = 0.18).
Conclusions:
- Genetic variations in the beta fibrinogen gene, specifically the Hd2 allele, are associated with higher plasma fibrinogen levels.
- These genetic differences may contribute to the higher prevalence of elevated fibrinogen and potentially increased CHD risk observed in Caucasian populations compared to Japanese populations.
Abstract:
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)