Genetic predictors of an unfavorable course of obliterating atherosclerosis of lower limb arteries

Abstract

AIM: This study aimed to determine the influence of −250G>A polymorphism in the LIPC gene and –1607insG in the MMP-1 gene on the course of obliterating atherosclerosis of lower limb arteries (OALLA).

MATERIALS AND METHODS: Seventy-six individuals were included in this study. In the first group (n = 34), patients with an unfavorable (progressive) course of OALLA and developed critical ischemia of the lower limbs within 5 years from the onset of the disease were included. In the second group (n = 34), patients with a conventionally favorable (non-progressive) course but did not develop critical ischemia of the lower limbs within 5 years from the onset of the disease and did not have a progressive degree of chronic ischemia. In the control group, healthy volunteers (n = 8) without signs of atherosclerosis in all vascular pools were included. In all the patients, LIPC-250G>A and MMP-1-1607insG were genotyped. The difference in the observed and expected frequencies was evaluated via a Pearson χ2 test with correction for likelihood.

RESULTS: Significant differences (p = 0.013) in the −250G>A polymorphism of the LIPC gene were found between the observed and expected frequencies compared with those in patients with OALLA and healthy volunteers. The assessment of the first and second groups revealed differences in the observed and expected frequencies (р = 0.004). Heterozygous carriage (GA genotype) was associated with an increased risk of the development of the unfavorable course of OALLA (hazard ratio = 2.133 with 95% confidence interval = 1.214–3.748). In the analysis of the −1607insG polymorphism of the MMP-1 gene, statistically insignificant data were obtained compared between the first and second groups (р = 0.128) and between the groups of patients with OALLA and healthy volunteers (р = 0.38).

CONCLUSIONS: The heterozygous carrier of LIPC −250G>A was associated with an increased risk of an unfavorable OALLA course. This research on this polymorphism could be applied to patients with the newly diagnosed atherosclerosis of the arteries of the lower extremities to determine the prognosis of the disease course, especially in young patients with early manifestation and individuals with a burdened hereditary history. The −1607insG polymorphism of the MMP-1 gene had no effect on the course of OALLA.

Keywords

atherosclerosis / critical ischemia / disease course prediction / genetic predictors / polymorphism / LIPC-250G>A / MMP-1-1607insG

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