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

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.

Relationship Between Calcium-phosphorous Product, Native and Bioprosthetic Mitral Valve Calcifications

“…Despite this, BPV still fail, especially in a mitral position (30% degeneration at 12-15 years), mainly due to degradation and calcification. Stabilization of tissues by glutaraldehyde promotes cell death, and it has been shown that its activity persists for many months after implantation, slowly releasing active glutaraldehyde monomers that destroy fibrocytes and macrophages that come into contact with the toxic material [10][11][12][13][14][15][16].…”

Inherited Variation in Cytokine, Acute Phase Response, and Calcium Metabolism Genes Affects Susceptibility to Infective Endocarditis

“…The procedures of DNA extraction and genotyping were the same as previously described [ 12 , 25 – 27 ]. Briefly, 5 mL of venous blood was collected into a tube with ethylenediaminetetraacetic acid.…”

Polymorphisms Within Innate Immune Response, Calcium Metabolism and Lipid Metabolism Are Predictors of Infective Endocarditis

“…Выделение ДНК и генотипирование прово-дилось аналогично предыдущим работам на-шей научной группы [15,16,23,28]. В таблице 3 приведены специфичные праймеры для гено-типирования.…”

“…Статистический анализ проводился аналогич-но предыдущим работам нашей научной группы [15,16,23,28] с применением программ GraphPad Prism (GraphPad Software) и SNPStats [31].…”

“…Развитие и клини-ческое течение ИЭ могут зависеть от: 1) опозна-вания патоген-ассоциированных молекулярных паттернов, цитокинового и острофазового отве-та [16,25,35]; 2) гемостаза [5,21,24]; 3) липидно-го [13,22] и кальциевого профиля плазмы крови [30,32]. Концептуально процессы воспаления, окисления липидов, кальцификации и гемоста-за в настоящее время рассматриваются как взаи-мосвязанные в рамках иммуновоспалительного континуума, одним из конечных звеньев кото-рого является кальцификация нативных и про-тезных клапанов сердца, ведущая к клапанной деструкции и недостаточности [28].…”