The association of 17q23.1 locus with advanced carotid atherosclerosis

In this study, we analyzed the association of rs8078424 (chr17:59873104) with the risk of advanced carotid atherosclerosis and disease-related traits. We also assessed the association of this genetic variant with the expression of MIR21 gene in peripheral blood leukocytes of patients. Methods. A group of cases included patients with advanced carotid atherosclerosis who had artery stenosis with 80% or more by ultrasound examination (n=104). We used two control groups. Resident population of Tomsk was the first group (n=161). A second group consists of relatively healthy individuals who had non-hemodynamically significant carotid atherosclerosis (24% or less; n=84). Genotyping of rs8078424 was performed using MALDI-TOF mass spectrometry on a Sequenom MassARRAY® (USA) platform. The expression level of the MIR21 gene in peripheral blood leukocytes was assessed by droplet digital PCR on a QX200 Droplet Digital PCR System (Bio-Rad). Results. The GG rs8078424 genotype was found to be protective against of advanced carotid atherosclerosis (OR=0.023, 95%CI:0.08-0.62; p=0.003) and associated with a lower level of total cholesterol in the serum and increased MIR21 gene expression in peripheral blood leukocytes of the patients. Potential molecular mechanisms of the association of rs8078424 with atherosclerosis include alteration of transcription factors binding sites (FOXP1, SOX18, GATA3, HOXD9, HOXD10, and C/EBPalpha) as well as relationship with the MIR21 gene expression in cells of target organs. Conclusion. The polymorphism of the 17q23.1 locus (in the region of the TUBD1, VMP1/MIR21 genes) is of interest for a more detailed study of susceptibility to cardiovascular diseases in the context of epigenetic mechanisms in single cells of the target organs.

carotid atherosclerosis, rs8078424, total cholesterol level, miR-21

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