Impact of polymorphisms in the alpha- and beta-fibrinogen gene on plasma fibrinogen concentrations of coronary heart disease patients.
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 alpha-fibrinogen gene and HaeIII, HindIII and BclI in the beta-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%).(ABSTRACT TRUNCATED AT 250 WORDS)
Heinrich
J
J
Institute of Clinical Chemistry, University of Münster, Germany.
Funke
H
H
Rust
S
S
Schulte
H
H
Schönfeld
R
R
Köhler
E
E
Assmann
G
G
D000483:Alleles; D001483:Base Sequence; D003327:Coronary Disease / Q000097:blood*; D005340:Fibrinogen / Q000032:analysis / Q000235:genetics*; D005787:Gene Frequency; D005796:Genes; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length
D005340:Fibrinogen