engleski

POLYMORPHISM OF PARAOXONASE GENES IN CROATIAN POPULATION WITH ATHEROSCLEROTIC VASCULAR DISEASE (ZAGREB COHORT)

BACKGROUND: Human serum paraoxonase (PON1) is an esterase coded by pon1 gene located on the chromosome 7 and linked with two other PON-like genes. Several polymorphisms of the pon1 and pon2 genes (L55M, -108C>T, Q192R and S311C) are associated with the risk of atherosclerotic vascular disease (AVD). The aim of this study was to determine the association between these polymorphisms and AVD in a Zagreb cohort- Croatian population. METHODS: 226 native Croatians were classified into two groups: 73 healthy controls and 153 subjects with clinically and angiografically confirmed AVD (71 with >70% stenosis of cerebral arterias and 82 with peripheral stenosis). Each peripheral stenosis was scored according to the criteria of hemodynamic significance in a total of 21 peripheral arteries: 0 = normal ; 1 = < 50% stenosis, 2 = 50-99% stenosis and 3 = occlusion. The total sum of scores was determined as an angiographically "Mercury" score as a unique measure of the anatomical extent of atherosclerotic lesions. Polymorphisms of the pon1 and pon2 genes were determinated using polymerase chain reaction- restriction length polymorphism analysis (PCR- RFLP) accredited under the requirements of the standard 15189. RESULTS: In a Zagreb cohort- Croatian population compared to healthy controls cases with >70% of cerebral (p=0, 285 for L55M ; p=0, 921 for S311C) as well as peripheral stenosis (p=0, 327 for L55M ; p=0, 875 for S311C) had similar genotype and allele frequencies of L55M polymorphism of the pon1 and S311C polymorphism of pon2 gene. In cases with >70% of cerebral stenosis similar genotype and allele frequencies of Q192R and -108C>T polymorphisms of the pon1gene were found (p=0, 925 for Q192R ; p=0, 746 for -108C>T) compared to healthy controls. Cases with peripheral stenosis had significantly higher QQ genotype (p<0, 001) and higher Q allele frequency of Q192R (p=0, 007) compared to healthy controls. Although in cases with peripheral stenosis no significantly higher C allele frequency of -108C>T was found (p=0, 857), the CC genotype distribution was much more frequent (p<0, 001). CONCLUSIONS: Although the data in recent studies have been inconsistent, our results in a Zagreb cohort-Croatian population indicate a significant association of Q192R polymorphism with peripheral stenosis.

POLYMORPHISM OF PARAOXONASE GENES; ATHEROSCLEROTIC VASCULAR DISEASE

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