The association of I/D polymorphism of ACE gene with metabolic factors of cardiovascular risk, structural and functional state of left cardiac chambers in patients with diabetic nephropathy and essential hypertension

Abstract

Objective — to reveal an association of I/D polymorphism of ACE gene with metabolic factors of cardiovascular risk (CVR) such as visceral obesity (VO), insulin resistance (IR), dyslipidemia (DLP) as well as with indices characterized structural and functional state of left cardiac chambers in patients (pts) with diabetic nephropathy (DN) and essential hypertension (EH).
 Materials and methods. The investigation was conducted at the Clinical Department of Arterial Hypertensions and Kidney Diseases in L. T. Mala National Therapy Institute of NAMS of Ukraine (Kharkiv). Clinical examinations involved 82 pts, 42 (51.2 %) females and 40 (48.8 %) males with DN of I — IV stage and EH of II — III stage, aged 31 to 82 years old (an average age is (61.65 ± 1.28) years old). Three genotypes of I/D polymorphism of ACE gene included II — 18 (24.7 %), ID — 32 (43.8 %) and DD — 23 (31.5 %) of cases correspondingly were investigated in 73 (89.0 %) pts. Anthropometric measurements with calculations of body mass index (BMI), body fat percentage (BFP), body fat mass (BFM), fat mass index (FMI) were conducted by known formulas in all pts. Blood lipids were detected by enzyme method with measuring of total cholesterol, high‑density lipoprotein cholesterol (HDL‑C) and triglycerides (TG). Levels of cholesterol of very low density and low‑density lipoprotein (VLDL‑C, LDL‑C) were calculated by standard formulas. Blood glucose level was measured by glucose oxidase method and serum insulin was detected by immunoassay method. IR indices such as HOMA‑IR, triglyceride glucose index (TGGI) and METS‑IR (metabolic score for insulin resistance) were obtained by known formulas. I/D polymorphism of ACE gene (rs 4646994) was investigated with a usage of polymerase chain reaction. Structural and functional state of left cardiac chambers was estimated using transthoracic echocardiography. Systolic and diastolic blood pressure (SBP and DBP) were measured by Korotkov’s method. The results were statistically obtained with computer programs Microsoft Office Excel 2003 and Statistica 23.0.
 Results. In pts with II genotype, LDL‑C levels positively correlated with BFP (r = 0.490; p = 0.046) and BFM (r = 0.484; p = 0.049) in conditions with hypertriglyceridemia due to activation of visceral fat lipolysis in which a reverse correlation between relative thickness of left ventricle wall (RTLVW) and serum TG concentration (r = –0.540; p = 0.02) could be explained. In pts with ID genotype, presence of D allele in genotype was associated with an increase in RTLVW due to SBP influence (r = 0.358; p = 0.045). In genotype ID there was a relationship between IR index HOMA‑IR and BMI (r = 0.399; p = 0.029) and HOMA‑IR and FMI (r = 0.402; p = 0.025) that demonstrated VO participation of in the development of IR in pts with DN and EH and genotype ID. In pts with DN and EH, who had DD genotype, SBP level reversely correlated with HDL‑C (r = –0.498; p = 0.018) that could be explained by influence of IR on elevation of SBP and reduction of HDL‑C. In pts with DD genotype both SBP and DBP almost equally influenced on the left atrial diameter (r = 0.460; p = 0.036 and r = 0.453; p = 0.034 correspondingly). In pts with DN and EH whose had DD genotype IR index METS‑IR positively correlated with RTLVW (r = 0.419; p = 0.047) and left ventricle myocardial mass index (r = 0.518; p = 0.011) that confirmed an association of D allele of ACE gene with left ventricle hypertrophy caused both by EH and IR.
 Conclusions. It has been established that in patients with diabetic nephropathy and essential hypertension, the I/D polymorphism of ACE gene was associated with such metabolic factors of cardiovascular risk as visceral obesity, insulin resistance, dyslipidemia, and pathological left ventricle remodeling.