The association of rs1799983 eNOS gene polymorphism with dyslipidemia and efficacy of atorvastatin in correction of lipid exchange disorders in patients with diabetic nephropathy and essential hypertension

Abstract

Objective — to search an association of rs1799983 endothelial nitric oxide synthase (eNOS) gene polymorphism with dyslipidemia (DLP) and the efficacy of atorvastatin used in correction of lipid exchange disorders in patients with diabetic nephropathy (DN) and essential hypertension (EH).
 Materials and methods. The study had been conducted in the clinical Department of Arterial Hypertension and Kidney Disease at L. T. Mala National Therapy Institute of NAMS of Ukraine (Kharkiv). Clinical examinations involved 89 patients (pts) (43(48.3%) females and 46(51.7%) males) with DN of II—IV stages and EH of II—III stages aged 34 to 78 years old (an average age is 57.11±1.89 years old). They were also genotyped for rs1799983 eNOS gene polymorphism (G894T) with a use of polymerase chain reaction. GG genotype was revealed in 29(32.6%) of pts, GT genotype was found in 33(37.1%) of cases and 27(30.3%) participants of the study had TT genotype. With the use of immune enzyme method, serum levels of total cholesterol (TC), high‑density lipoprotein cholesterol (HDL‑C) and triglycerides (TG) were measured in all included pts. Very low density lipoprotein cholesterol (VLDL‑C), low‑density lipoprotein cholesterol (LDL‑C), non‑HDL‑C and coefficient of atherogenicity were calculated by known formulas. Atorvastatin was prescribed to all the pts included in study for correction of lipid exchange disorders in daily doses of 10—20 mg (an average daily dose was 16.7±0.91 mg) for 24 weeks.
 Results. Rs1799983 eNOS gene polymorphism in pts with DN and EH was found to be associated with lipid parameters characterized a phenotype of diabetic DLP with its peculiar disorders in the systems of reverse cholesterol transport and lipoprotein lipolysis of TG‑containing VLDL. In this case a dominant G allele was associated with less significant lipid disorders than a recessive T allele. A homozygous state with allele G (genotype GG) in pts with DN and EH was associated with abnormalities in the system of TG‑containing VLDL lipolysis and an appearance of T allele in genotype (genotypes GT and TT) made an additional negative contribution to the state of lipid exchange and transport. In pts with genotype GT abnormalities in reverse cholesterol transport added to disorders in the system of TG‑containing VLDL lipolysis and in pts with genotype TT there was a combination of disorders in the systems of direct, reverse cholesterol transport and lipoprotein lipolysis. The study of hypolipidemic effects of atorvastatin depended on genotype of rs1799983 eNOS gene polymorphism showed that in GG genotype atorvastatin demonstrated mainly a hypocholesterolemic action while in genotypes contained T allele (GT and TT) we observed a reduction of hypocholesterolemic effect against the background of significant hypotriglyceridemic action and elevation of HDL‑C.
 Conclusions. In pts with DN and EH rs1799983 eNOS gene polymorphism was associated with diabetic DLP. A recessive allele T was associated with significant lipid disorders compared with a dominant G allele. A significant hypocholesterolemic effect of atorvastatin was observed in case of a presence of G allele in pts genotype while a presence of T allele in pts genotype (GT and TT) was associated with a reduction of atorvastatin cholesterol lowering action.