To access this material please log in or register

Register Authorize

Prevalence of rs10519210, rs1739843, and rs6787362 polymorphisms in patients with CHF of ischemic origin

Tishkova V. M., Prokopova L. V., Kostareva A. A., Sitnikova M. Yu.
Federal State Budgetary Institution "Federal Almazov North-West Medical Research Center" of the Ministry of Health of the Russian Federation, Akkuratova 2, St. Petersburg 197341

Keywords: heart failure, coronary heart disease, genetic cardiology, myocardial infarction, ejection fraction

DOI: 10.18087/rhfj.2017.2.2318

Background. Genome-wide association studies (GWAS) can identify patients with increased risk of HF after MI and facilitate development of preventive measures. Aim. To study prevalence of polymorphous alleles of HSPB7 (rs1739843), FRMD4B (rs6787362) genes and the 15q22 (rs10519210) locus associated with the HF syndrome as had been demonstrated by GWAS on a large sample of EU residents, in residents of the North-Western Federal District of the Russian Federation. Materials and methods. Men aged 30–65 who had had MI more than 3 months ago, were evaluated. The main group consisted of 260 patients with FC I–IV HF, LV EF (Simpson) <40%; the reference group included 96 donors. Results. The groups were comparable in the duration of AH (11.4 vs. 11.2 years) but different in the AH prevalence (68.5 and 83.3%; р<0.01). The main group contained more patients with complicated family history (34.23 and 22.88%; р<0.01), atrial fibrillation (AF) (31.2 and 14.4%; p<0.001), pulmonary artery thromboembolism (12.5 and 0.4%; р<0.001), and LV aneurism (20.6 and 0.9%; р<0.001). In the HF group with low EF, the QRS complex was wider (124.6±259.4 and 96.9±53.1ms; р<0.001) and pulmonary artery pressure was higher (46.3±48.7 and 30.2±24.8 mm Hg, р<0.001). Prevalence of the HSPB7В gene rs1736843 polymorphism was significantly different depending on the presence of HF and LV EF; in the main group, the CC genotype was found in 48.1% of patients and ТТ – in 10.4% of patients; in the reference group – in 80.9 and 7.3%; and in healthy subjects – in 80.2 and 4.2% of cases, respectively (p1–2, 1–3 <0.001). Prevalence of the FRMD4B gene also exceeded the significance threshold. In the main group, the AA genotype was observed in 83.5% of patients and GG in none of them; in the reference group – in 87.8 and 2.9%; and in healthy subjects – in 89.6 and 0%, respectively (p1–2, 3–2 <0.01). Prevalence of the USP3 gene did not differ between the study groups.
  1. Cambien F, Tiret L. Genetics of cardiovascular diseases: from single mutations to the whole genome. Circulation. 2007;116(15):1714–24. DOI:10.1161/CIRCULATIONAHA.106.661751.
  2. Laird NM, Lange C. Family-based designs in the age of large-scale gene-association studies. Nat Rev Genet. 2006;7(5):385–94. DOI:10.1038/nrg1839.
  3. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447(7145):661–78. DOI:10.1038/nature05911.
  4. Krief S, Faivre JF, Robert P, Le Douarin B, Brument-Larignon N, Lefrère I et al. Identification and characterization of cvHsp. A novel human small stress protein selectively expressed in cardiovascular and insulin-sensitive tissues. J Biol Chem. 1999;274(51):36592–600.
  5. Golenhofen N, Perng MD, Quinlan RA, Drenckhahn D. Comparison of the small heat shock proteins alphaB-crystallin, MKBP, HSP25, HSP20, and cvHSP in heart and skeletal muscle. Histochem Cell Biol. 2004;122(5):415–25. DOI:10.1007/s00418-004-0711-z.
  6. Klarlund JK, Holik J, Chawla A, Park JG, Buxton J, Czech MP. Signaling complexes of the FERM domain-containing protein GRSP1 bound to ARF exchange factor GRP1. J Biol Chem. 2001;276(43):40065–70. DOI:10.1074/jbc.M105260200.
  7. Chishti AH, Kim AC, Marfatia SM, Lutchman M, Hanspal M, Jindal H et al. The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane. Trends Biochem Sci. 1998;23(8):281–2.
  8. Pearson MA, Reczek D, Bretscher A, Karplus PA. Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain. Cell. 2000;101(3):259–70.
  9. Davie AP, Francis CM, Caruana L, Sutherland GR , McMurray JJ. Assessing diagnosis in heart failure: which features are any use? QJM. 1997;90(5):335–9.
  10. Mant J, Doust J, Roalfe A, Barton P, Cowie MR , Glasziou P et al. Systematic review and individual patient data meta-analysis of diagnosis of heart failure, with modelling of implications of different diagnostic strategies in primary care. Health Technol Assess. 2009;13(32):1–207. DOI:10.3310/hta13320.
  11. Oudejans I, Mosterd A, Bloemen JA, Valk MJ, van Velzen E, Wielders JP et al. Clinical evaluation of geriatric outpatients with suspected heart failure: value of symptoms, signs, and additional tests. Eur J Heart Fail. 2011;13(5):518–27. DOI:10.1093/eurjhf/hfr021.
  12. Fonseca C. Diagnosis of heart failure in primary care. Heart Fail Rev. 2006;11(2):95–107. DOI:10.1007/s10741-006-9481-0.
  13. Kelder JC, Cramer MJ, van Wijngaarden J, van Tooren R , Mosterd A, Moons KGM et al. The diagnostic value of physical examination and additional testing in primary care patients with suspected heart failure. Circulation. 2011;124(25):2865–73. DOI:10.1161/CIRCULATIONAHA.111.019216.
  14. Stark K, Esslinger UB, Reinhard W, Petrov G, Winkler T, Komajda M et al. Genetic association study identifies HSPB7 as a risk gene for idiopathic dilated cardiomyopathy. PLoS Genet. 2010;6(10):e1001167. DOI:10.1371/journal.pgen.1001167.
  15. Matkovich SJ, Van Booven DJ, Hindes A, Kang MY, Druley TE, Vallania FLM et al. Cardiac signaling genes exhibit unexpected sequence diversity in sporadic cardiomyopathy, revealing HSPB7 polymorphisms associated with disease. J Clin Invest. 2010;120(1):280–9. DOI:10.1172/JCI39085.
  16. Barlassina C, Dal Fiume C, Lanzani C, Manunta P, Guffanti G, Ruello A et al. Common genetic variants and haplotypes in renal CLCNKA gene are associated to salt-sensitive hypertension. Hum Mol Genet. 2007;16(13):1630–8. DOI:10.1093/hmg/ddm112.
  17. Sile S, Velez DR , Gillani NB, Alexander CA, Alexander CR, George AL et al. Haplotype diversity in four genes (CLCNKA, CLCNKB, BSND, NEDD4L) involved in renal salt reabsorption. Hum Hered. 2008;65(1):33–46. DOI:10.1159/000106060.
  18. Hawkins PT, Anderson KE, Davidson K, Stephens LR . Signalling through Class I PI3Ks in mammalian cells. Biochem Soc Trans. 2006;34(Pt 5):647–62. DOI:10.1042/BST0340647.
Tishkova V. M., Prokopova L. V., Kostareva A. A., Sitnikova M. Yu. Prevalence of rs10519210, rs1739843, and rs6787362 polymorphisms in patients with CHF of ischemic origin. Russian Heart Failure Journal. 2017;18 (2):115–121

To access this material please log in or register

Register Authorize
Ru En