The frequency of the -455G/A fibrinogen promoter polymorphism in a neonatal cohort

Abstract

Fibrinogen is a protein produced by the liver, and found circulating in the blood. It plays a major role in the binding of platelets following vascular injury, and the formation of blood clots by its conversion to insoluble fibrin fibres. It is coded for by 3 different genes, FGA, FGB and FGG, on chromosome 4. Several sites displaying polymorphic variations have been identified in recent years, and attempts have been made to correlate these with fibrinogen levels in the blood. The -455G/A (rs1800790) (NC_000004.11:g.155483708G>A) is one such polymorphism, which has been linked to higher fibrinogen levels. In a recent study performed on the local MAMI (Maltese Acute Myocardial Infarction) collection, the SNP (Single Nucleotide Polymorphism) was not found to be in Hardy-Weinberg equilibrium (HWE). This project aimed to identify its frequency in an unbiased, consecutive neonatal cohort, by testing DNA from cord blood collected over a 3 month period during the summer of 2010. This involved DNA extraction from the white blood cell fraction of the cord blood, Polymerase Chain Reaction (PCR) amplification of the region carrying the polymorphism, Restriction Enzyme (RE) Digestion by the HaeIII enzyme, and separation and visualisation of DNA fragments via agarose gel electrophoresis. The resulting allele frequencies (0.76 for the major allele and 0.24 for the minor allele) were comparable to those reported in other European populations, although deviation from Hardy-Weinberg equilibrium was again observed in the neonatal cohort tested.