Peripheral arterial disease (PAD) is characterized by insufficient delivery of oxygenated blood to the peripheral tissues, which in most cases is caused by atherosclerosis. PAD usually affects arteries of the lower limbs. As a result of insufficient blood circulation, patients develop cramping pain in the leg muscles. These patients have a greater risk for other cardio-vascular events, because PAD is in most cases a consequence of generalized atherosclerosis. The measurement of the ankle-brancial index (ABI) is used for the diagnosis of the disease. In the case of advanced PAD (critical limb ischemia or disturbing cramping pain), revascularization should be performed. Percutaneous transluminal angioplasty (PTA) is used to treat shorter narrowing, which despite its good primary performance is limited by the development of restenosis.
The development of PAD is influenced by risk factors and genetic predisposition. It has been proven that ABI is largely inherited, but it is not yet known for which genetic changes. We aimed to investigate the association between polymorphisms rs12803, rs146608 and rs13428968 of the NR4A2 gene, rs668 and rs12953 of the PECAM1 gene, rs10499563 of the IL6 gene and rs10861032 on chromosome 12 and PAD, cardio-vascular events and restenosis after PTA. To this end, we have set two surveys. In study A we enrolled 662 patients with PAD and 615 patients without PAD, while in study B there were 182 PTA patients. DNA sections, where polymorfisms are located, were multiplied with real-time PCR and genotypes were determined by allelic distrimination. We found that the studied polymorphisms are not more frequent in patients with PAD compared to peers without disease. In the patients distribution to those who suffered a cardio-vascular event and those without an event, we found that the polymorphisms rs668 of the PECAM1 gene, rs10499563 of the IL6 gene, rs10861032 on chromosome 12 and the haplotype 4 in PECAM1 are weakly associated with frequency of cardio-vascular events. GG genotype in polimorphism rs668 was associated with a 1.5-fold higher risk for a major event, TT genotype in rs10499563 was associated with a 1.6-fold higher risk for a minor event, CC genotype in rs10861032 was associated with a 2,4-fold higher risk for any event or with 2.6-fold higher risk for a minor event, and haplotype 4 in PECAM1 was associated with a 2.9-fold higher risk for any or a 3.9-fold higher risk for a minor event. Polymorphisms rs12803, rs146608 and rs13428968 of the NR4A2 gene was not associated with the frequency of cardio-vascular events. With restenosis after PTA was weakly associated polymorphisms rs668 of the PECAM1 gene and rs10499563 of the IL6 gene. GG genotype in polymorphism rs668 was associated with a 1.9-fold lower risk, and TT genotype in polymorphism rs10499563 was associated with a 2.3-fold higher risk. Polymorphisms rs12803, rs146608 and rs13428968 of the NR4A2 gene, rs12953 of the PECAM1 gene and rs10861032 on chromosome 12 was not associated with restenosis after PTA. The absence of association of some polymorphisms in candidate genes with PAD, cardio-vascular events and restenosis could be a consequence of the actual absence of association or the characteristics of the subjects. These processes are influenced by many risk factors. To determine the association of polymorphisms as independent risk factors, these factors should also be taken into account in statistical data processing. Considering that only weak links were found, findings should be confirmed on a larger group of subjects. It would also be meaningful to investigate the association between the interaction of polymorphisms with the development of PAD, cardio-vascular events and restenosis.
|
