Angiotensin-converting enzyme gene polymorphism, lipids, and apolipoproteins in menopausal women on hormone replacement therapy.Acta Med Croatica 2001; 55(4-5):161-7AM
This study investigated the frequency of angiotensin-converting enzyme (ACE) genotypes, concentrations of total cholesterol (T-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein Lp (a), Established Risk Factor (ERF) ratio (total cholesterol/HDL-C), apolipoproteins A-I, A-II, apoBand apoE in 134 menopausal women aged 49.62 +/- 4.83 on oral hormone replacement therapy (HRT) (2 mg 17 beta estradiol plus 1 mg norethisterone acetate/day), during (mean +/- SD) 15.77 +/- 9.94 months. ACE genotypes of 134 menopausal women showed DD genotype in 48 (36%), ID genotype in 59 (44%), and II genotype in 27 (20%) women, with the mean body mass index (BMI) (kg/m2) of 26.34 +/- 4.02, systolic blood pressure (mm Hg) of 145.71 +/- 23.32, diastolic blood pressure of 95.28 +/- 12.88, pulse rate of 77.76 +/- 13.81, positive family history of myocardial infarction (MI) (23%) and stroke (22%); 26% were smokers and 6% consumed alcohol regularly. The mean levels of TC (mmol/l) were 5.72 +/- 1.25, TG (mmol/L) 1.63 +/- 0.82, HDL-C (mmol/L) 1.15 +/- 0.29, LDL-C (mmol/L) 3.98 +/- 1.31, lipoprotein Lp(a) (g/L) 0.16 +/- 0.24, ERF ratio 5.35 +/- 1.90, apolipoproteins (g/L): A-I 1.83 +/- 0.39, A-II 0.57 +/- 0.12, apoB 0.92 +/- 0.31, and apoE 0.08 +/- 0.04. The highest mean levels of T-C 5.89 +/- 1.40, TG 1.67 +/- 0.96, LDL-C 4.15 +/- 1.60, lipoprotein Lp(a) 0.19 +/- 0.25) apoB 0.95 +/- 0.32 and ERF ratio 5.46 +/- 2.24 were found in ID genotype, while in DD genotype HDL-C 1.11 +/- 0.28 and apo A-I 1.78 +/- 0.34 were lowest. In II genotype, the levels of apo A-II 0.56 +/- 0.11 were lowest and of apoE 0.09 +/- 0.05 highest. According to DD, ID and II genotypes and lipid, lipoprotein Lp(a), ERF ratio and apolipoprotein concentrations, there were no statistically significant differences between groups. ERF ratio in DD genotype showed a positive correlation with TG (r = 0.59) and LDL-C (r = 0.57), a slight positive correlation with apoB (r = 0.40), and a strong negative correlation with HDL-C (r = -0.73). ERF in ID genotype showed a strong negative correlation with HDL-C (r = -0.73), strong positive correlation with TG (r = 0.70), and T-C (r = 0.58), and slight positive correlation with LDL-C (r = 0.36) and alcohol abuse (r = 0.34). In II genotype, ERF ratio showed a strong positive correlation with LDL-C (r = 0.73), T-C (r = 0.70) and apoE (r = 0.58), slight positive correlation with apoB (r = 0.46) and TG (r = 0.36), and negative correlation with HDL-C (r = -0.54). Matrix correlation of DD genotypes showed the highest positive correlation between T-C and LDL-C (r = 0.91) and apoE (r = 0.45), and negative correlation between HDL-C and ERF ratio (r = 77), and LDL-C and ERF ratio (r = 0.55). In ID genotype, T-C showed a strong positive correlation between LDL-C (r = 0.75) and ERF ratio (r = 0.63), TG and ERF ratio (r = 0.73), and negative with HDL-C (r = 0.53). In genotype II, T-C showed a strong positive correlation between LDL-C (r = 0.96), ERF ratio (r = 0.71), apoB (r = 0.66) and apoE (r = 0.46). LDL-C correlated positively with ERF ratio (r = 0.72), apoB (r = 0.61) and apoE (r = 0.48). These findings indicated the frequency of ACE genotypes to differ within the group of menopausal women. Analysis of ACE genotypes showed ID genotype to be most common among menopausal women. This result indicated their intermediate risk of coronary heart disease (CHD) and myocardial infarction (MI). It has been well established that an increased risk of MI is associated with high frequency of DD genotype, and a low risk with high frequencies of II genotype. In addition to ACE polymorphism analysis, assessment of lipid, apolipoprotein, and lipoprotein Lp(a) concentrations, and of ERF ratio provides further important parameters for better understanding of the risk factors for CDH in women. In the present study, assessment of the genetic, metabolic and environmental markers pointed to an intermediate risk of CHD in menopausal women on HRT, although the mechanism underlying the disease is not clear and well understood yet.