Get Adobe Flash player

OPTIMIZING THE PREVENTION OF CORONARY HEART DISEASE IN PATIENTS WITH RHEUMATOID ARTHRITIS DEPENDING ON GENOTYPE OF GLUCOCORTICOID RECEPTOR GENE BCL1 POLYMORPHISM

Аuthors: O. V. Savchenko

Pages: 786–793

Abstract

         

Purpose. The purpose of our review is to justify the ischemic heart disease (IHD) prevention in individuals with rheumatoid arthritis (RA) depending on Bcl1 polymorphism of glucocorticoid receptor (GR) gene.

Patients and methods. Study involved 76 RA patients with no concomitant cardiovascular diseases aged over 40 as well as 96 healthy individuals. In the research, we used routine examination of RA diagnosis, SCORE scale, biochemical and molecular genetic methods (polymerase chain reaction with the following analysis of restriction fragments’ length by Fleury I. et al., 2003). Atorvastatin dosage was adjusted according to the guidelines of Association of Cardiologists of Ukraine, 2011. Statistical analysis of the obtained results was conducted using SPSS-17 software.

Results and discussion. To evaluate the efficiency of IHD prevention in patients with RA, we considered the average levels of low-density lipoprotein cholesterol (LDL-C) depending on the Bcl1 polymorphism of GR gene. The dynamics of LDL-C concentration was evaluated after 4 weeks. We estimated its target content considering cardiovascular risk by SCORE scale. The study revealed that after 4 week treatment with atorvastatin, LDL-C level in RA patients with C/C genotype decreased by 20.9 %, with C/G – by 10 % and with G/G – by 3 %. Considering that LDL-C level had not decreased to the target concentration in 16 (21.1 %) homozygous carriers of the G allele, their dosage of atorvastatin was doubled for another 4 weeks. This resulted in adequate decrease of LDL-C level.

Conclusions. Treatment of RA patients with G/G genotype of Bcl1 polymorphism of GR gene with the double recommended dose of atorvastatin considering cardiovascular mortality risk by SCORE scale provides for required LDL-C level within 4 weeks if started from the beginning of treatment period. Such approach makes it possible to improve IHD prevention in individuals with RA.

Keywords: rheumatoid arthritis, ischemic heart disease, low-density lipoprotein cholesterol, Bcl1 polymorphism, glucocorticoid receptor.

This email address is being protected from spambots. You need JavaScript enabled to view it.

The full text

To view the full text

References

  1. Popkova TV, Novikova DS, Nasonov EL Ateroskleroz pri revmaticheskih zabolevaniyah. V kn.: Revmatologiya: klinicheskie rekomendatsii. M.: GEOTAR-Media. 2010: 678.
  2. Peters MJ, Symmons DP, McCarey DW et al. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other types of inflammatory arthritis — TASK FORCE «Cardiovascular risk management in RA». Ann Rheum. Dis. 2010; 69 (2): 325−331.
  3. Hramtsova NA, Dzizinskiy AA. Ishemicheskaya bolezn serdtsa pri revmatoidnom artrite: faktoryi riska, osobennosti techeniya i kliniko-patogeneticheskie vzaimosvyazi s aktivnostyu vospaleniya. Sibirskiy meditsinskiy zhurnal. 2011; 6 (105): 46–48.
  4. Kropotina TV, Morova NA, Gudinova ZhV, Kokuhina NS. Faktoryi riska i prognozirovaniya razvitiya serdechno-sosudistyih zabolevaniy u bolnyih revmatoidnyim artritom. Sibirskiy meditsinskiy zhurnal. 2013; 3: 72−76.
  5. Gerli Bartoloni R, Bocci E, Sherer Y et al. Association of anti-cyclic citrullinated peptide antibodies with subclinical atherosclerosis in patients with rheumatoid arthritis. Ann Rheum. Dis. 2008; 67: 724−725.
  6. Lopez-Longo FJ, Oliver-Minarro D, de la Torre I et al. Association between anti-cyclic citrullinated peptide antibodies and ischemic heart disease in patients with rheumatoid arthritis. Arthr. Rheum. 2009; 61: 419−424.
  7. Danninger K, Hoppe UC, Pieringer H. Do statins reduce the cardiovascular risk in patients with rheumatoid arthritis? Ann Rheum. Dis. 2015; 74 (8): 1544−1550.
  8. Nikitina NM, Rebrov AP. Effektyi atorvastatina u bolnyih revmatoidnyim artritom s dislipidemiey. Klinitsist. 2011; 1: 47−53.
  9. Aydeniz A, Sever T, Pehlivan S et al. Investigation of glucocorticoid receptor gene Bcl1 polymorphism in rheumatoid arthritis. Turkish J. Rheumatology. 2011; 26 (3): 199–203.
  10. Di Blasio AM, van Rossum EF, Maestrini S et al. The relation between two polymorphisms in the glucocorticoid receptor gene and body mass index, blood pressure and cholesterol in obese patients. J. Steroid Biochem. Mol. Biol. 2009; 113 (3–5): 269–274.
  11. Popovic B, Macut D, Isailovic T et al. Bcl1 polymorphysm of glucocorticoid receptor gene in coronary artery disease. Endocrine Abstracts. 2010; 22: 169.
  12. Mitchenko OI, Lutai MI. Dyslipidemii: diahnostyka, profilaktyka ta likuvannia. Kyiv, 2011. 48 s.
  13. Fleury I, Beaulieu P, Primeau M et al. Characterization of the BclI Polymorphismin the Glucocorticoid Receptor Gene. Clinical. Chemistry. 2003; 49 (9): 1528–1531.
  14. Novikova DS, Popkova TV, Nasonov EL. Snizhenie kardiovaskulyarnogo riska pri revmatoidnom artrite: dvoynaya polza statinov. Nauchno-prakticheskaya revmatologiya. 2010; 6: 61−71.
  15. Kuriata OV, Sirenko OIu. Dobovyi profil arterialnoho tysku, lipidnyi spektr krovi u khvorykh na arterialnu hipertenziiu v poiednanni z revmatoidnym artrytom ta efektyvnist zastosuvannia atorvastatynu. Simeina medytsyna. 2015; 3 (59): 155–159.
  16. Komendantova NS, Kulakov YuV, Sinenko AA, Lukyanov PA. Vozmozhnosti primeneniya atorvastatina u bolnyih revmatoidnyim artritom s giperholesterinemiey. Tihookeanskiy meditsinskiy zhurnal. 2015; 4: 37−38.
  17. McCarey DW, McInnes IB, Madhok R et al. Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial. Lancet. 2004; 363: 2015–2021.
  18. Smakotina SA, Zelendinova AR, Bondareva IN, Berns SA. Pleiotropic effects of atorvastatin in rheumatoid arthritis patients with no history of cardiovascular diseases. Ter. Arkh. 2015; 87 (9): 72−76.
  19. Akiyama M, Mawatari T, Nakashima Y. et al. Prevalence of dyslipidemia in Japanese patients with rheumatoid arthritis and effects of atorvastatin treatment. Clin. Rheumatol. 2015; 34 (11): 1867−1875.
  20. Koeijvoets KCMC, van der Net JB, van Rossum EFC et al. Endocrine research two common haplotypes of the glucocorticoid receptor gene are associated with increased susceptibility to cardiovascular disease in men with familial hypercholesterolemia. Home. 2008; 93 (12): 4902–4908.
  21. Numakura K, Kagaya H, Yamamoto R et al. Characterization of Clinical and Genetic Risk Factors Associated with Dyslipidemia after Kidney Transplantation. Hindawi Publishing Corporation Disease Markers. 2015. http://dx.doi.org/10.1155/2015/179434.
  22. Kovalenko VN, Kuchmenko EB, Mhitaryan LS. Rol odinochnyih nukleotidnyih polimorfizmom i mikro RNK v patogeneze zabolevaniy serdechno-sosudistoy sistemyi. Zhurnal NAMN UkraYini. 2014; 20(1): 62−73.
  23. Panchyshyn YuM, Komarytsia OI. PCSK9, mikrosomnyi tryhlitserydtransportnyi protein i hen ANGPTL3 yak prychyny dyslipoproteinemii ta nova mishen yikh likuvannia. Ratsyonalnaia farmakoterapyia. 2013; 2: 19−21.
  24. Van Venrooij FV, Stolk RP, Banga JD et al. Common cholesteryl ester transfer protein gene polymorphisms and the effect of atorvastatin therapy in type 2 diabetes. Diabetes Care. 2003; 26: 1216−1223.

Purpose. The purpose of our review is to justify the ischemic heart disease (IHD) prevention in individuals with rheumatoid arthritis (RA) depending on Bcl1 polymorphism of glucocorticoid receptor (GR) gene.

Patients and methods. Study involved 76 RA patients with no concomitant cardiovascular diseases aged over 40 as well as 96 healthy individuals. In the research, we used routine examination of RA diagnosis, SCORE scale, biochemical and molecular genetic methods (polymerase chain reaction with the following analysis of restriction fragments’ length by Fleury I. et al., 2003). Atorvastatin dosage was adjusted according to the guidelines of Association of Cardiologists of Ukraine, 2011. Statistical analysis of the obtained results was conducted using SPSS-17 software.

Results and discussion. To evaluate the efficiency of IHD prevention in patients with RA, we considered the average levels of low-density lipoprotein cholesterol (LDL-C) depending on the Bcl1 polymorphism of GR gene. The dynamics of LDL-C concentration was evaluated after 4 weeks. We estimated its target content considering cardiovascular risk by SCORE scale. The study revealed that after 4 week treatment with atorvastatin, LDL-C level in RA patients with C/C genotype decreased by 20.9 %, with C/G – by 10 % and with G/G – by 3 %. Considering that LDL-C level had not decreased to the target concentration in 16 (21.1 %) homozygous carriers of the G allele, their dosage of atorvastatin was doubled for another 4 weeks. This resulted in adequate decrease of LDL-C level.

Conclusions. Treatment of RA patients with G/G genotype of Bcl1 polymorphism of GR gene with the double recommended dose of atorvastatin considering cardiovascular mortality risk by SCORE scale provides for required LDL-C level within 4 weeks if started from the beginning of treatment period. Such approach makes it possible to improve IHD prevention in individuals with RA