VII Международная студенческая научная конференция Студенческий научный форум - 2015

The beneficial effects of statins are the result of their capacity to reduce cholesterol biosynthesis, mainly in the liver, where they are selectively distributed, as well as to the modulation of lipid metabolism, derived from their effect of inhibition upon HMG-CoA reductase. Statins have anti-atherosclerotic effects that positively correlate with the percent decrease in LDL cholesterol. In addition, they can exert anti-atherosclerotic effects independently of their hypolipidemic action. Because the mevalonate metabolism generates a series of isoprenoids vital for different cellular functions, from cholesterol synthesis to the control of cell growth and differentiation, HMG-CoA reductase inhibition has beneficial pleiotropic effects. Consequently, statins reduce significantly the incidence of coronary events, both in primary and secondary prevention, being the most efficient hypolipidemic compounds that have reduced the rate of mortality in coronary patients. Independent of their hypolipidemic properties, statins interfere with events involved in bone formation and impede tumor cell growth.

Atorvastatin is a synthetic hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. In dosages of 10 to 80 mg/day, atorvastatin reduces levels of total cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride and very low-density lipoprotein (VLDL)-cholesterol and increases high-density lipoprotein (HDL)-cholesterol in patients with a wide variety of dyslipidemias. Atorvastatin has a much longer plasma half-life period of 18-24 hours than other statins and has additional antioxidant property. Simvastatin is lipophilic and given in lactone precursor form. In dosages of 5 to 80 mg/day, a greater rise in HDL cholesterol level is resulted. Oral absorption is better and is of half-life period of 2-3 hours.

PURPOSE OF THE RESEARCH:

1. To study the carriers of allelic variants of MDR1 gene on the locus C3435T protein-convertor of statins by glycoprotein-R and their impact on hypolipidemic effect of statins in patients with coronary heart disease (CHD) with isolated and combined hyperlipidemia high density lipoprotein (HDL).

2. To compare the effectiveness of lipid lowering with atorvastatin and simvastatin in correction of the isolated and combined hyperlipedemia HDL in patients with coronary heart disease.

MAIN BACKGROUND OF THE RESEARCH:

Interindividual variability in drug response is a major clinical problem and is of concern during drug development. Statins, such as atorvastatin, are taken orally and access to their site of action in the liver is greatly facilitated by both intestinal and hepatic transporters. Allelic gene’s impact on the effectiveness of statins.

MATERIALS AND METHODS:

The observation is of 43 patients with isolated and combined hyperlipidemia high density lipoprotein aged from 51 years to 60 years of age and with 22 patients in the control group. Serum lipid levels were determined at baseline with the help of laboratory analysis and identification of MDR1 C3435T polymorphisms was performed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

In the process of studying the data sample family history and excluded patients with diseases that cause the secondary lipid disorders.

CONTROL GROUP: The control group (non-pharmacological interventions) included patients who had contraindications or adverse drug reactions (ADRs), which developed in the application of statins, and patients who refuse hypolipidemic correction for economic reasons. The control group was comparable to the basic satisfaction featured with the intervention group.

RESULTS OBTAINED:

Patients were divided into groups of intervention. In the intervention group which is treated with simvastatin of dosage 40 mg/day and in patients treated with atorvastatin of dosage 20mg/day following spectrum of allelic genes are obtained:

In the patients taking atorvastatin, revealed a smaller effect on indicators of total cholesterol, low density lipoprotein, cholesterol and atherogenic index among patients with homozygotes for the version cytosine – cytosine, heterozygotes was compared with the group of homozygotes thymine – thymine.

Table 1. Comparison of drug’s effect on the allelic genes:

Spectrum of allelic genes	Simvastatin 40 mg/day	Atorvastatin 20 mg/day
Homozygotes cytosine-cytosine (C-C)	11-25.6 %	12-28.6 %
Heterozygotes cytosine-thymine (C-T)	22- 51.1%	21-50.0%
Homozygotes thymine-thymine (T-T)	10-23.3 %	9-21.4 %

According to this comparing study results it is clear that the atorvastatin efficacy to hypolipidemic effect is higher in the patients with homogenous thymine-thymine.

Graph 1. LDL lowering and Allelic genes.

According to this graphical study it is clear that the efficacy of atorvastatin is higher in lowering the lipoprotein when compared with simvastatin.

Atorvastatin caused significantly greater reductions from baseline than did simvastatin for LDL cholesterol, total cholesterol, very low density lipoprotein cholesterol, triglycerides, and apolipoprotein B (p < 0.05). With atorvastatin 20 mg, 46% of the patients achieved LDL cholesterol target goal, whereas only 27% of the simvastatin patients achieved the target goal at the 40-mg dose.

Conclusion:

1. Study of the association between the options of MDR1 on allelic C3435T show the dominance of the sick with great effect among patients homozygous for option TT compared with the groups of heterozygotes and homozygotes CC in both groups on indicators for total cholesterol, LDL cholesterol, AI .

2. The most effective was pharmacotherapy atorvastatin dose of 20 mg/day in groups of patients – homozygotes TT.

3. Atorvastatin caused significantly greater reductions from baseline than did simvastatin for LDL cholesterol, total cholesterol, very low density lipoprotein cholesterol, triglycerides.

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