SPECIFICS OF LIPID METABOLISM AND ATORVASTATIN EFFICACY IN TYPE 2 DIABETES WITH CARRIAGE OF VARIOUS POLYMORPHISMS OF CHOLESTEROL ETHER CARRYING PROTEIN TaqIB GENE

Aim. To assess the specifics of lipid metabolism and efficacy of atorvastatin therapy in Saint-Petersburg citizens, having 2 type diabetes (DM2) — the carriers of various TaqIB gene polymorphisms, the cholesterol ethers transporting protein (CETP).

Material and methods. Totally 382 patients studied, with DM2, native for statins, and 187 almost healthy individuals. All participants underwent blood sampling with lipids test and molecular-genetic testing. Into atorvastatin group we included 164 patients with DM2 and dyslipidemia. Lipid profile parameters were assessed at baseline and in 3 months of atorvastatin therapy.

Results. In almost healthy individuals the carriage of B1B2 genotype of TaqIB polymorphism of CETP gene is associated with higher levels of triglycerides, low density lipoproteides cholesterol, very low density cholesterol and atherogenity coefficient, comparing to these values in B2B2 carriers. DM2 patients had higher triglycerides level if B1B1 comparing to B2B2. In DM2 type, triglycerides level also was higher in B1B1 than in B2B2 (p=0,044); other lipid spectrum parameters did not differ between two groups. While comparing the efficacy of atorvastatin therapy in various genotypes carriers of TaqIB polymorphism gene CETP, there were no differences of the studied parameters within treatment. While evaluating the target levels reach of lipid spectrum on the atrovastatin therapy it was found, that only B1B1 carriers reached target triglycerides level (p=0,017).

Conclusion. In DM2 patients the arrangement of genotypes and alleles of TaqIB polymorphism of CETP gene did not differ of this in healthy individuals; in carriers of different genotypes of this gene lipidogram parameters at baseline and on treatment by atorvastatin for 3 months did not differ; in B1B1 carriers the levels of triglycerides reached target values on atorvastatin.

1. Kim MV, Skoryukova SA, Bystrova AA, et al. Paraoxonase 1 gene polymorphisms in patients with type 2 diabetes mellitus. Record of the I. P. Pavlov St. Petersburg State Medical University 2014; 2: 69-72. Russian (Ким М. В., Скорюкова С. А., Быстрова А. А. и др. Полиморфизм Q192R гена параоксоназы 1 у больных сахарным диабетом 2 типа. Ученые записки СПбГМУ им. Акад. И. П. Павлова 2014, 2: 69-72).

2. Wander GS, Aston CE, Sanghera DK. Genetic variation in cholesterol ester transfer protein, serum CETP activity, and coronary artery disease risk in Asian Indian diabetic cohort. Pharmacogenet Genomics 2012; 22: 95-104.

3. Thompson A, Di Angelantonio E, Sarwar N, et al. Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk. JAMA 2008; 299: 2777-88.

4. Linsel-Nitschke P, Tall AR. HDL as a target in the treatment of atherosclerotic cardiovascular disease. Nat. Rev. Drug Discov. 2005; 4: 193-205.

5. Shakhtshneider EV, Kulikov IV, Maksimov VN, et al. CETP gene polymorphism in the caucasian population of West Siberia and in groups contrast by total serum cholesterol levels. Bull. Exp. Biol. Med. 2014; 157: 364-7.

6. Zhijun Wu, Yuqing Lou, Xiaochun Qiu, et al. Association of cholesteryl ester transfer protein (CETP) gene polymorphism, high density lipoprotein cholesterol and risk of coronary artery disease: a meta-analysis using a Mendelian randomization approach. BMC Medical Genetics 2014; 15: 182.

7. Ikewaki K, Mabuchi H, Teramoto T, et al. Association of cholesteryl ester transfer protein activity and TaqIB polymorphism with lipoprotein variations in Japanese subjects. Metabolism 2003; 52: 1564-70.

8. Li TY, Zhang C, Asselbergs FW, et al. Interaction between dietary fat intake and the cholesterol ester transfer protein TaqIB polymorphism in relation to HDL-cholesterol concentrations among US diabetic men. Amer. J. Clin. Nutr. 2007; 86: 1524-9.

9. Moroshkina NV, Bogdanova MA, Ignatyeva OI, et al. Protein gene Taq IB polymorphism transferring Сholesterol ester of men with coronary artery disease. Vestnik of Saint Petersburg university 2008; 11: 39-46. Russian (Морошкина Н. В., Богданова М. А., Игнатьева О. И. и др. TaqIB полиморфизм гена белка, переносящего эфиры холестерина, у мужчин с ишемической болезнью сердца. Вестник Санкт-Петербургского университета 2008, 11: 39-46).

10. Rahimi Z, Nourozi-Rad R, Vaisi-Raygani A, et al. Association between cholesteryl ester transfer protein TaqIB variants and risk of coronary artery disease and diabetes mellitus in the population of western Iran. Genet Test Mol Biomarkers 2011; 15: 813-9.

11. Li J, Zhang L, Xie NZ, et al. Relationship between the cholesterol ester transfer protein TaqIB polymorphism and the lipid-lowering effect of atorvastatin in patients with coronary atherosclerotic heart disease. Genet Mol Res. 2014; 13: 2140-8.

12. Maitland-van der Zee AH, Boerwinkle E. Pharmacogenetics of response to statins: where do we stand?. Curr Atheroscler Rep. 2005; 7: 204-8.

13. Siewert S, Gonzalez II, Lucero RO, et al. Association of cholesteryl ester transfer protein genotypes with paraoxonase-1 activity, lipid profile and oxidative stress in type 2 diabetes mellitus. Journal of Diabetes Investigation 2014; 10: 3-11.