Local vascular immune response is primarily initiated via Toll-like receptors (TLRs) and triggering receptor expressed on myeloid cells-1 (TREM-1). We previously showed that certain TLR and TREM-1 gene polymorphisms are associated with coronary artery disease (CAD). Therefore, we hypothesized that these gene polymorphisms are associated with atherosclerosis severity. This study included 292 consecutive patients with CAD who were admitted to the Research Institute for Complex Issues of Cardiovascular Diseases (Kemerovo, Russian Federation) during 2011–2012. Sample genotyping was performed in 96-well format using the TaqMan SNP genotyping assay. We found that C/C genotype of the rs3804099 polymorphism within TLR2 gene and T/T genotype of the rs4711668 polymorphism within TREM-1 gene were significantly associated with severe coronary atherosclerosis while C allele of the rs5743551 polymorphism within TLR1 gene, A/G genotype of the rs4986790 polymorphism and C/T genotype of the rs4986791 polymorphism within TLR4 gene, and C allele of the rs3775073 polymorphism within TLR6 gene were significantly associated with severe noncoronary atherosclerosis. However, A/A genotype of the rs5743810 polymorphism within TLR6 gene was significantly associated with mild noncoronary atherosclerosis. We conclude that certain TLR and TREM-1 gene polymorphisms are significantly associated with atherosclerosis severity in a Russian population.
Valvular calcification precedes the development of valvular stenosis and may represent an important early phenotype for valvular heart disease. It is known that development of valvular calcification is likely to occur among members of a family. However, the knowledge about the role of genomic predictive markers in valvular calcification is still elusive. Aims of this review are to assess the impact of gene polymorphisms on risk and severity of aortic stenosis and mitral annular calcification. According to the results of the investigations carried out, all polymorphisms may be divided into the three groups conferring the level of evidence of their association with valvular stenosis. It is possible to conclude that apoB (XbaI, rs1042031, and rs6725189), ACE (rs4340), IL10 (rs1800896 and rs1800872), and LPA (rs10455872) gene polymorphisms may be associated with valvular calcific stenosis with a relatively high level of evidence. A number of other polymorphisms, such as PvuII polymorphism within the ORα gene, rs1042636 polymorphism within the CaSR gene, rs3024491, rs3021094, rs1554286, and rs3024498 polymorphisms within the IL10 gene, rs662 polymorphism within the PON1 gene, rs2276288 polymorphism within the MYO7A gene, rs5194 polymorphism within the AGTR1 gene, rs2071307 polymorphism within the ELN gene, rs17659543 and rs13415097 polymorphisms within the IL1F9 gene may correlate with a risk of calcific valve stenosis with moderate level of evidence. Finally, rs1544410 polymorphism within the VDR gene, E2 and E4 alleles within the apoE gene, rs6254 polymorphism within the PTH gene, and rs1800871 polymorphism within the IL10 gene may be associated with aortic stenosis with low level of evidence.
Severe bioprosthetic mitral valve calcification is a significant problem in cardiovascular surgery. Unfortunately, clinical markers did not demonstrate efficacy in prediction of severe bioprosthetic mitral valve calcification. Here, we examined whether a genomics-based approach is efficient in predicting the risk of severe bioprosthetic mitral valve calcification. A total of 124 consecutive Russian patients who underwent mitral valve replacement surgery were recruited. We investigated the associations of the inherited variation in innate immunity, lipid metabolism and calcium metabolism genes with severe bioprosthetic mitral valve calcification. Genotyping was conducted utilizing the TaqMan assay. Eight gene polymorphisms were significantly associated with severe bioprosthetic mitral valve calcification and were therefore included into stepwise logistic regression which identified male gender, the T/T genotype of the rs3775073 polymorphism within the TLR6 gene, the C/T genotype of the rs2229238 polymorphism within the IL6R gene, and the A/A genotype of the rs10455872 polymorphism within the LPA gene as independent predictors of severe bioprosthetic mitral valve calcification. The developed genomics-based model had fair predictive value with area under the receiver operating characteristic (ROC) curve of 0.73. In conclusion, our genomics-based approach is efficient for the prediction of severe bioprosthetic mitral valve calcification.
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