Impact of polymorphisms in the alpha- and beta-fibrinogen gene on plasma fibrinogen concentrations of coronary heart disease patients

Abstract

Despite many investigations in a variety of experimental settings, uncertainty remains concerning the size of the genetic contribution to plasma fibrinogen levels. We used the polymerase chain reaction to amplify the polymorphic sites for the restriction enzymes TaqI in the α-fibrinogen gene and HaeIII, HindIII and BclI in the β-fibrinogen gene. Three hundred and eighty-four male coronary heart disease patients were investigated. Two alleles for each enzyme (+ or − designating, respectively, the presence or absence of the cutting site) were detected. The HaeIII and HindIII cutting sites were in complete linkage disequilibrium. A small but significant increase in fibrinogen level was associated with the rare cutting sites of HaeIII HindIII , BclI and TaqI. At all polymorphic sites homozygosity for the frequent alleles was associated with about 0.20 g/l lower plasma fibrinogen concentrations than heterozygosity at the respective sites (p < 0.05). The frequencies and natures of the rare alleles were as follows: TaqI (+) 0.28, HaeIII HindIII (−) 0.22 and BclI (+) 0.17. Mean fibrinogen levels in patients heterozygous for each of the four polymorphisms were 0.47 g/l greater than in subjects homozygous for the frequent allele at each cutting site ( HaeIII HindIII + −, TaqI + −, BclI + ÷ fibrinogen level 3.58 g/l (n = 32); HaeIII HindIII + +, TaqI − −, BclI − ÷ fibrinogen level 3.11 g/l (n = 99), p = 0.003). Each polymorphism accounted for between 0.5 and 1.4% of the overall variance in fibrinogen concentration. Together, the polymorphisms in HaeIII, HindIII and TaqI explained 5.8% of overall variance, a proportion equivalent to that explained by age, smoking and body mass index (5.5%). In conclusion, there is a hereditary component to plasma fibrinogen concentrations in men. Individuals predisposed to increased fibrinogen levels can be detected using restriction fragment length polymorphisms.