Genetic predisposition to calcific aortic stenosis and mitral annular calcification

Abstract

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.

Effect of Two Lipoprotein (a)-Associated Genetic Variants on Plasminogen Levels and Fibrinolysis

“…LPA SNPs rs3798220 and rs10455872 are consistently associated with Lp(a) levels and result in increased risk for cardiovascular diseases (Arsenault et al 2014; Clarke et al 2009; Kutikhin et al 2014; Thanassoulis et al 2013). In the present study, we investigated the effects of these variants not only on their impact on Lp(a) levels but also on their potential effect on thrombogenicity in order to provide novel insights regarding the mechanism(s) by which LPA variants confer CVD susceptibility.…”

“…LPA SNPs rs3798220 and rs10455872 are consistently associated with Lp(a) levels and result in increased risk for cardiovascular diseases (Arsenault et al 2014; Clarke et al 2009; Kutikhin et al 2014; Thanassoulis et al 2013). However, the mechanism of action behind these two genetic variants previously implicated in CVD risk is not known.…”

Genotypes and Serum Levels of Apolipoprotein E and Paraoxonase 1 in Calcific Aortic Valve Stenosis

“…There is a concept that CAVS is a genetically determined disease; gene candidates of this pathology have been reported sporadically [8]. Our hypothesis is that some alleles of the apoE and PON1 genes, along with the changes in concentrations of these substances, may cause development of CAVS.…”

The genetic background of calcific aortic valve disease: retrospective study

“…Проблема генетической предрасположенности к КБАК в последнее время активно изучается. На основании результатов нескольких десятков исследований выделены генетические полиморфизмы с высокой, умеренной и низкой степенью доказанности влияния на риск развития кальциноза АК [3]. Из рассматриваемых генетических маркеров в метаанализе участвовал лишь полиморфизм rs662 гена SPP1, который был отнесен к группе с умеренной ассоциативной связью с КБАК, что не нашло подтверждения в нашем исследовании.…”