Polymorphic Causes of Atherosclerosis

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p22phox protein, the allelic variants of 242C/T, and the mRNA are expressed in the form of human blood vessels. The production of basal and NADH-derived superoxide in blood vessels was variable. The CYBA 242T allele was associated with a reduced activity of NAD(P)H oxidase activity, free from any other clinical risks factors precipitating atherosclerosis. Patients having genotypes of CC, TT, or CT were isolated. Their RT-PCR products were subjected to restriction analysis and sequencing. This confirmed the expression of alleles in every case. This allelic expression was found to be according to the genotype determined using genomic DNA. It was found that the internal mammary artery also contained p22phox, C/T variants, and mRNA. The data confirmed the presence of p22phox protein in saphenous vein and proved that the expression of C/T allele in the blood vessels is in correspondence with the genotype.

The results compiled by Ishigami et al. (1995) showed that the frequencies of genotypes aa, Aa, and AA in the patients with an underlying coronary disease were 65.9%, 26.8%, and 7.3%, respectively. The corresponding frequencies in the control group were found to be 49.3%, 31.9%, and 18.8%, respectively. The occurrence of “a” allele was in excess. The study concluded by establishing a significant link between the development of coronary atherosclerosis and the molecular variant of the angiotensinogen gene, suggesting the molecular variant as a likely risk factor for coronary atherosclerosis.

Zhang et al. (1999) detected an unreported yet common type of polymorphism in the gene encoding gelatinase B. This polymorphism has risen because of a transition in thymidine from cytosine at the position 1562. The DNA-protein interaction assay and transient transfection processes indicated that the promoter activity in T allele was greater as compared to C allele. This increase in the promoter activity was because the putative transcription repressor bound preferentially to the C allelic promoter. No significant differences were found between the case and control subjects in terms of allele frequencies. The study concluded that the functional genetic variation has a direct influence on the promoter activity of gelatinase B activity and has a greater effect on the atherosclerotic phenotype.

Discussion

Various theories have been proposed in terms of polymorphisms as a genetic cause of atherosclerosis. The findings of the research by Guzik et al. (2000) suggest that CYBA-242T allele is linked with NAD(P)H oxidase in both maximal and basal conditions. The mechanism of the effects and their consequences of atherosclerosis is not clear. Ishigami et al. (1995) have highlighted another possible mechanism of how polymorphism can cause atherosclerosis. This research particularly emphasized on the polymorphism observed in angiotensinogen gene and established the importance of ACE activity in the thickening of carotid wall. It was further suggested that it as an important risk factor for coronary atherosclerosis. Zhang et al. (1999) discussed a completely different polymorphic mechanism responsible for the initiation of atherosclerosis. He argued that gelatinase B, a proteolytic metalloproteinase can undergo polymorphism, particularly in its promoter region to affect the atherosclerotic phenotypes. The future research can involve studying larger samples with a greater variety of participants in order to establish a better relationship with the genotypic and phenotypic indications of atherosclerosis. The approach has a potential for better understanding the non-genetic factors in addition to the polymorphic genetic changes leading to atherosclerosis.