Spectrum and prevalence of prothrombotic single nucleotide polymorphism profiles in the Greek Cypriot population.

BACKGROUND: This study was performed to establish the allele, genotype and genotype combination/SNP (single nucleotide polymorphism) profile frequencies in the general population of Cyprus for 6 genes implicated in thrombotic disorders. The genes with their respective functional polymorphisms were the following: factor V (G1691A), prothrombin/factor II (G20210A), methylenetetrahydrofolate reductase (C677T), platelet glycoprotein receptor IIIa (P1A1/A2), b-fibrinogen (G/A-455) and plasminogen activator inhibitor-type 1 (4G/5G). METHODS: DNA samples from 121 unrelated individuals were used for this epidemiological study. The polymerase chain reaction followed by restriction digestion were used to genotype the 6 different polymorphic loci. Allele and genotype frequencies were established and shown to be in Hardy-Weinberg equilibrium. RESULTS: Mutant allele frequencies for the 6 genes were as follows: factor V-4%, prothrombin-2%, methylenetetrahydrofolate reductase -39%, platelet glycoprotein receptor IIIa-16%, beta-fibrinogen-17% and plasminogen activator inhibitor - type 1-46%. Combined defects occurred which may increase the risk for vascular events, 33% of individuals (39/118) had 3 or more of the above mutations. CONCLUSIONS: As in other European populations, prospective case-control studies to estimate the risk for deep vein thrombosis (DVT) and ischemic episodes with respect to genetic and environmental risk factors should be performed. Thrombophilia screening should be applied for primary and secondary prevention of thrombotic episodes in susceptible individuals on the island of Cyprus. Individuals targeted for such screening include those with the following: a positive family history for thrombosis; a previous DVT or other ischemic episode; prior exposure to circumstantial risk factors and in the presence of echolucent plaques.

Geographical clustering of low density lipoprotein receptor gene mutations (C292X; Q363X; D365E & C660X) in Cyprus.

In Cyprus, no data are yet available on the frequencies of clinically diagnosed FH patients. Further, until now, familial hypercholesterolaemia in Cyprus had not been studied at the molecular level to determine the nature or frequency of LDLR gene mutations. Being a relatively homogeneous population, we anticipated that a few founder mutations would predominate on the island. In the present study, three previously identified LDLR gene mutations were found to cosegregate with high LDL cholesterol levels in 23 unrelated, clinically diagnosed families with FH. Geographical clustering of each of these LDLR gene mutations was indicated, a phenomenon arising from low migration rates and high inbreeding. The latter cultural practices account for the discovery of a homozygous FH sib pair whose parents are carriers of the same mutation. Microsatellite and intragenic haplotype analysis in this FH population, suggested that the families which shared the same LDLR gene mutation have a common origin. This is supported by their relative geographical distribution. Thirty young FH individuals were also offered presymptomatic diagnosis which should facilitate the prevention of premature coronary artery disease. Finally, results from this study support the suggestion that the formation of tendon xanthomata in FH patients may be under environmental influence. Hum Mutat 15:380, 2000.