A Genomics-Based Model for Prediction of Severe Bioprosthetic Mitral Valve Calcification.

Anastasia Ponasenko,Natalia Kondyukova,Arseniy Yuzhalin,Anton Kutikhin,Leonid Barbarash,Anna Tsepokina,Natalia Rutkovskaya,Maria Khutornaya

doi:10.3390/ijms17091385

Abstract

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.

Highlights

Mitral valve calcification, accompanied by inflammation and lipid deposition, is associated with common cardiovascular risk factors and represents an important risk factor of mitral valve disease [1,2]
We identified eight single nucleotide polymorphisms (SNPs) being significantly associated with severe bioprosthetic mitral valve calcification (Table 1)
The C allele of the rs1800796 polymorphism within the TLR6 gene, the T allele of the rs1205 polymorphism within the CRP gene, and the G allele of the rs10455872 polymorphism within the LPA gene were associated with decreased risk of severe bioprosthetic mitral valve calcification

Summary

Introduction

Mitral valve calcification, accompanied by inflammation and lipid deposition, is associated with common cardiovascular risk factors and represents an important risk factor of mitral valve disease [1,2]. Bioprosthetic mitral valves frequently undergo severe calcification which is able to cause bioprosthetic valve failure and may require repeated valve replacement surgery, a major clinical intervention [1]. Mitral valve calcification is frequent among family members [6] but genomic markers of native and bioprosthetic mitral valve calcification are still almost unknown [7]. Their identification may assist in revealing the underlying mechanisms of these conditions. We investigated whether SNPs within innate immunity, lipid metabolism and calcium metabolism genes are significant predictors of severe bioprosthetic mitral valve calcification

Results

Discussion

Population

Statistical Analysis