Molecular Biology Reports

, Volume 41, Issue 9, pp 5645–5663

Genetic predisposition to calcific aortic stenosis and mitral annular calcification

  • Anton G. Kutikhin
  • Arseniy E. Yuzhalin
  • Elena B. Brusina
  • Anastasia V. Ponasenko
  • Alexey S. Golovkin
  • Olga L. Barbarash
Article

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.

Keywords

Valvular calcification Heart valves Aortic stenosis Mitral annular calcification Gene polymorphisms Genetic predisposition 

Abbreviations

SNP

Single nucleotide polymorphism

VDR

Vitamin D receptor

apo

Apolipoprotein

LDL

Low-density lipoprotein

TGF

Transforming growth factor

ORα

Oestrogen receptor alpha

OR

Odds ratio

CI

Confidence interval

IL

Interleukin

ACE

Angiotensin-converting enzyme

PTH

Parathormone

CaSR

Calcium-sensing receptor

CTGF

Connective tissue growth factor

FGF

Fibroblast growth factor

PON

Paraoxonase

MYO7A

Myosin VIIA

AGTR

Angiotensinogen receptor

ELN

Elastin

LPA

Lipoprotein(a)

GALTN2

Polypeptide N-acetylgalactosaminyltransferase 2

LPL

Lipoprotein lipase

ABCA1

ATP-binding cassette sub-family A member 1

APOA5

Apolipoprotein A-V

SCARB1

Scavenger receptor class B member 1

LIPC

Hepatic triglyceride lipase

CETP

Cholesterol ester transfer protein

LCAT

Lecithin-cholesterol acyltransferase

LIPG

Endothelial triglyceride lipase

APOC4

Apolipoprotein C-IV

PLTP

Phospholipid transfer protein

HDL

High-density lipoprotein

PCR–RFLP

Polymerase chain reaction–restriction fragment length polymorphism

KIV-2

Kringle IV type 2

GWAS

Genome-wide association studies

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Anton G. Kutikhin
    • 1
    • 2
    • 3
  • Arseniy E. Yuzhalin
    • 4
  • Elena B. Brusina
    • 1
    • 3
  • Anastasia V. Ponasenko
    • 1
  • Alexey S. Golovkin
    • 1
  • Olga L. Barbarash
    • 1
  1. 1.Research Institute for Complex Issues of Cardiovascular Diseases Under the Siberian Branch of the Russian Academy of Medical SciencesKemerovoRussian Federation
  2. 2.Central Research LaboratoryKemerovo State Medical AcademyKemerovoRussian Federation
  3. 3.Department of EpidemiologyKemerovo State Medical AcademyKemerovoRussian Federation
  4. 4.Department of Oncology, Cancer Research UK and Medical Research Council Oxford Institute for Radiation OncologyUniversity of OxfordOxfordUK

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