Effect of Apolipoprotein E Genotype on Association of Menopausal Status with Lipid Level in Japanese Women

Abstract

Serum lipid level increases during hormonal transition before and after menopause. In Caucasians, changes in lipid level after menopause across apolipoprotein E (apo E) genotypes were studied. We investigated 159 Japanese healthy female workers (age range, 35-63). The apo E genotypes were determined by the polymerase chain reaction single-strand conformation polymorphisms method for the entire apo E-coding region. The low-density lipoprotein cholesterol (LDL-cholesterol) level significantly varied according to the apo E genotype, but not according to the menopausal status after adjusting for age and body mass index (p < 0.001). The effect of menopause on LDLcholesterol level significantly varied depending on the apo E genotype (p < 0.05). Apo E2 [APOE, R158C] carriers in the senium period had a lower LDL-cholesterol level than those in the fertile period (81.5 ± 12.0 mg/dl vs. 122.3 ± 12.9 mg/dl). In contrast, apo E3 homozygotes in the senium period showed a higher LDL-cholesterol level than those in the fertile period (140.9 ± 7.0 mg/dl vs. 134.1 ± 6.1 mg/dl). The LDL-cholesterol levels of apo E4 [APOE, C112R] carriers were the similar for the two periods. These results indicate that the serum lipid control in perimenopausal women should be customized according to the apo E genotype for the promotion of women's health in Japan.Key words ---menopause, lipid levels, apolipoprotein E genotype, polymerase chain reaction-single strandard conformation polymorphism, Japanese women, low-density lipoprotein cholesterol caused by changes in blood lipid levels after sexhormone transition.1-4) It was reported that menopause causes increases in the levels of serum total cholesterol, low-density lipoprotein cholesterol (LDL-cholesterol), triglyceride and apolipoprotein B, as well as decreases in the levels of high-density lipoprotein cholesterol (HDL-cholesterol) and apolipoprotein AI.5-6) A recent survey in Japan, where the diet and lifestyles are different from those in North America, has also showed that the serum total cholesterol level (< 220 mg/dl) in 50.9% of women in their fifties exceeded the recommended level.7) However, the data were derived from a crosssectional survey, and the results may be confounded by age and factors other than menopause. Indeed, some women are normolipidemic even after menopause, which is not fully explained by the menopausal status and lifestyles. Genetic property would be another factor, but this is a poorly examined issue in studies of women and serum lipid levels.

Associations of blood selenium and serum lipid levels in Japanese premenopausal and postmenopausal women

“…For instance, genetic factors such as defects in apolipoprotein E could affect lipid levels differentially across age and menopause status. 15 Because some lipid parameters, including HDL-C and TGs, were not associated with fluctuations in Se levels with or without adjustment for the other potential covariates (Table 2), the existence of metabolically distinct populations may affect the results to some extent. Supposing that antioxidants were effective against genetically determined hypercholesterolemia, supplementary Se intake might be recommended, particularly for postmenopausal women with genetic predispositions.…”

“…15 For the purpose of this study, female workers aged 35 years and older who did not have any known chronic illness were selectively recruited to participate after providing oral or written informed consent at the start of the series of studies. Only one person refused to volunteer for this study; the participation rate was 99.5%.…”

“…This study was part of the Menopausal Japanese Women Study, and the original study was approved by the Ethics Review Committee of the Shinshu University School of Medicine. 15 …”

Gender Disparities In Optimal Lipid Control Among Patients with Coronary Artery Disease

“…The apoE gene polymorphism has been reported to be a significant predictor of the response of the LDL-C level to atorvastatin therapy in men, but not women 61) . Among Japanese women, apoE3 homozygotes have higher LDL-C levels in the senium period than in the fertile period and Apo E2 carriers have lower LDL-C levels in the senium period than in the fertile period 62) . These results indicate that lipid control in women, especially postmenopausal women, may be customized according to genotype.…”

Effect of APOE polymorphism on obesity and lipid profile in women of differing reproductive status

“…[22]. Among subjects in the postmenopausal group, LDL-C level was approximately 1.2 mmol/l higher in the APOE*4 carriers than in the APOE*2 carriers; the difference between these two genotypes was smaller in premenopausal women.…”