Naslov
Polymorphism of some atherosclerosis candidate genes in a Croatian healthy population

Autori
Topić, Elizabeta ; Ivanišević, Ana Maria ; Štefanović, Mario ; Žuntar, Irena

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
1st Alps-Adria meeting on human genetics-Programme and abstracts / Zergollern, Ljiljana - Zagreb : Hrvatsko društvo za humanu genetiku, 2000, 96-7

Skup
1st Alps-Adria meeting on human genetics

Mjesto i datum
Brijuni, Hrvatska, 14.04.2000. - 15.04.2000

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Apo E; MTHFR; PON1; Factor V-Leiden; atherosclerosis; RFLP-SSCP

Sažetak
Although the impact of many genetic and environmental factors on the genesis of atherosclerosis is well known, the contribution of individual genes to this process in particular populations has not yet been fully clarified. This study was undertaken to determine the frequency of some of the most important gene polymorphisms, which have been associated with atherosclerosis in the healthy general population of Croatia. Genotype distribution as well as allele frequencies of ApoE, MTHFR, Paraoxonase (PON1), and Factor V-Leiden genes was investigated in 184 apparently healthy Croatian individuals between 18 – 70 years. Genetic polymorphism of Apo E, MTHFR, and PON1 was investigated by PCR-RFLP method using restriction enzymes Cfo I, Hinf I, and Alw I, respectively. Polymorphism of Factor V-Leiden was determined by RFLP-SSCP method. The human Apo E gene with three common alleles (e2, e3, e4) coding for three isoforms E2, E3, E4 differ by a single amino acid substitution and binding affinity for Apo E receptor. The genotype distribution of E2/3, E2/4, E3/3, E3/4 and E4/4 was 11.1 %; 4.2 %; 77.8 %; 5.6 % and 1.4 %, respectively. The allele frequencies of E2, E3 and E4 were 7.6 %, 86.1 % and 6.3%, respectively. In European population, the allele e3 frequency ranges from 55% - 90%. The C677T MTHFR mutation identified as a risk factor for atherosclerosis results in decreased enzyme activity and re-methylation of homocysteine to methionine with subsequent accumulation of homocysteine. The genotype distribution of MTHFR mutation showed 0.7% of homozygous and 46.5 % of heterozygous mutations. The allele frequency of MTHFR(+) was 24.0 % and of MTHFR(-) 76.6%. In Caucasian population the MTHFR (+) frequency ranged between 5%-12%. PON1 Glu92Arg gene polymorphism correlate with PON activity. As part of the HDL complex, it was implicated in organophosphate detoxification and in LDL protection from peroxidation. The genotype distribution of A/A, A/B and B/B genotypes was 46.8%, 49.2% and 4.0%, respectively. The frequency of allele A and B was 71.4% and 28.6% respectively. In European population, the frequency of A allele is about 69%, and of B allele about 31%. Factor V-Leiden predisposes to venous thrombosis and central retinal vein occlusion. In the study group there were 91.0% of wt/wt, 7.2% of heterozygote and 1.8% of homozygote genotype. The frequency of Leiden allele was 5.4%. The allele frequency in European populations ranges between 2-15%, and increases from the north to the south. The results of our study are in concordance with the Central European population. The allele frequencies of all examined atherosclerosis genes are in Hardy-Weinberg equilibrium. Comparison of the results obtained in the Croatian cohort of 184 healthy volunteers with the other European populations, yielded no substantial ethnic difference for most of the alleles studied, except for the MTHFR allele.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA