Low-density lipoprotein and high-density lipoprotein cholesterol levels in relation to genetic polymorphisms and menopausal status: The Atherosclerosis Risk in Communities (ARIC) Study

Division of Epidemiology and Community Health, University of Minnesota, School of Public Health, 1300 South 2nd Street, Suite 300, Minneapolis, MN 55454, United States.
Atherosclerosis (Impact Factor: 3.99). 03/2008; 200(2):322-8. DOI: 10.1016/j.atherosclerosis.2007.12.045
Source: PubMed


Genes coding for proteins involved in lipid metabolism and, in women, menopausal status are independently associated with high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) levels. We examined whether the association between common functional genetic polymorphisms of apolipoprotein E (apoE Cys112Arg and Arg158Cys) gene and LDL-c levels, as well as the associations between the cholesteryl ester transfer protein (CETP TaqIB), hepatic lipase (LIPC C-514T), and lipoprotein lipase (LPL Ser447Stop) genes and HDL-c levels are significantly modified by menopausal status. Plasma lipid concentrations, genotype, and menopausal status were assessed across four examinations in a sample of Caucasian and African-American women (n=4652-4876) who were aged 45-64 years at baseline from the Atherosclerosis Risk in Communities (ARIC) Study. The association between LDL-c levels and the apoE gene, and HDL-c levels and the LIPC and LPL genes were not modified by menopausal status. The only statistically significant gene by menopause interaction was with the CETP gene on HDL-c concentrations (p=0.04). However, the significant CETP gene by menopause interaction was possibly due to chance because of multiple testing. Postmenopausal women who were carriers of the A allele of the CETP gene had approximately 0.7 mg/dL lower HDL-c levels than pre-/perimenopausal counterparts, whereas the opposite pattern of HDL-c (0.4 mg/dL higher HDL-c postmenopausally) was observed for the GG genotype. Overall, our data suggest that the decrease in endogenous estrogen as a result of menopause may independently affect lipoprotein concentration, but does not alter the effect on plasma lipids of some common genetic polymorphisms that regulate lipoprotein metabolism.

Full-text preview

Available from:
  • Source
    • "Differences in enzyme activities or in lipoprotein biology may explain racial disparities in triglycerides and HDL levels. Indeed, one genotype analysis in a large cohort of black and white women indicated that genetic polymorphisms in the cholesteryl ester transfer protein gene, lipoprotein lipase gene, or hepatic lipase gene correlate with HDL levels,14 and another study reported higher lipoprotein lipase mRNA levels in the subcutaneous fat of the obese blacks than of the obese whites.15 Age, education, social economic status, dietary pattern, and other environmental factors also differ widely by ethnicity16 and are likely contributors to the observed disparities. "
    [Show abstract] [Hide abstract]
    ABSTRACT: During screening for enrollment in a clinical trial, we noticed potential racial disparities in metabolic syndrome variables in women who responded to our study advertisement. We designed a nested observational study to investigate whether metabolic syndrome variables differed between non-Hispanic blacks and non-Hispanic whites. The cohort comprised of women who have met the preliminary clinical trial criteria (body mass index [BMI] 25-45, age 20-75 years, and no use of lipid-lowering medications or supplements). These women, including 116 blacks and 138 whites, provided fasting blood samples for analysis of serum lipid profile. Blacks had lower mean triglycerides (81.1 ± 3.3 mg/dL vs 140.6 ± 5.9 mg/dL; P < .0001), total cholesterol (176.1 ± 3.6 mg/dL vs 201.6 ± 3.3 mg/dL; P < .0001), and low-density lipoprotein (111.7 ± 3.3 mg/dL vs 128.2 ± 2.9 mg/dL; P < .001) and higher mean BMI (37.2 ± 0.5 vs 35.2 ± 0.5; P < .01) and diastolic blood pressure (82.4 ± 0.8 mmHg vs 79.4 ± 0.7 mmHg; P < .01) than whites. Only 7% of blacks, compared with 41% of whites, had triglycerides ≥150 mg/dL; as a result, fewer black women met metabolic syndrome criteria than white women. Additionally, in women with waist circumference ≥88 cm (N = 215), high-density lipoprotein was higher in blacks than in whites (48.3 ± 1.5 mg/dL vs 44.2 ±1.3 mg/dL; P < .05). Due to racial differences in blood lipids, current metabolic syndrome criteria may result in underestimation of cardiovascular risk in blacks.
    Full-text · Article · Mar 2013
  • Source
    • "The meta-analyse in 2008 suggested the minor allele (B2 allele) frequency in the Whites was the same as East Asian populations (0.42) [101], in accordance with 0.43 and 0.47 respectively in our AD participants and controls. We also found the effect of B2 allele or homozygous genotype on HDL-C more apparent in females, which was probably associated with modification of hormone in menopausal status [113]. Such genetic testing is limited by the fact that each sequence variant explains only a modest fraction of the variance (2% or less) in lipid levels [114]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives Accumulating evidence suggested that dysregulation of cholesterol homeostasis might be a major etiologic factor in initiating and promoting neurodegeneration in Alzheimer's disease(AD). ATP-binding cassette transporter A1(ABCA1)[ideographic comma]hepatic lipase (HL, coding genes named LIPC) and cholesteryl ester transfer protein (CETP) are important components of high-density lipoprotein (HDL) metabolism and reverse cholesterol transport(RCT) implicated in atherosclerosis and neurodegenerative diseases. In the present study, we will investigate the possible association of several common polymorphisms(ABCA1R219K, CETPTaqIB and LIPC-250 G/A) with susceptibility to AD and plasma lipid levels. METHODS: Case--control study of 208 Han Chinese(104 AD patients and 104 non-demented controls) from Changsha area in Hunan Province was performed using the PCR-RFLP analysis. Cognitive decline was assessed using Mini Mental State Examination (MMSE) as a standardized method. Additionally, fasting lipid profile and the cognitive testing scores including Wechsler Memory Scale(WMS) and Wisconsin Card Sorting Test (WCST) were recorded.Results and conclusionsWe found significant differences among the genotype distributions of these three genes in AD patients when compared with controls. But after adjusting other factors, multivariate logistic regression analysis showed only ABCA1R219K(B = -0.903, P = 0.005, OR = 0.405, 95%CI:0.217-0.758) and LIPC-250 G/A variants(B = -0.905, P = 0.018, OR = 0.405, 95%CI:0.191-0.858) were associated with decreased AD risk. There were significantly higher levels of high-density lipoprotein cholesterol(HDL-C) and apolipoproteinA-I in the carriers of KK genotype and K allele(P < 0.05), and B2B2 genotype of CETP Taq1B showed significant association with higher HDL-C levels than other genotypes(F = 5.598, P = 0.004), while -250 G/A polymorphisms had no significant effect on HDL-C. In total population, subjects carrying ABCA1219K allele or LIPC-250A allele obtained higher MMSE or WMS scores than non-carriers, however, no significant association was observed in AD group or controls. Therefore, this preliminary study showed that the gene variants of ABCA1R219K and LIPC-250 G/A might influence AD susceptibility in South Chinese Han population, but the polymorphism of CETPTaq1B didn't show any association in despite of being a significant determinant of HDL-C.
    Full-text · Article · Nov 2012 · Lipids in Health and Disease
  • Source
    • "HL activity is susceptible to variations in endogenous sexual steroids. Estrogenic steroids suppress HL activity, while androgenic steroids increase it [8,48]. The effect of the C514T polymorphism on HL activity is independent of androgen action [49]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hepatic lipase (HL), an enzyme present in the hepatic sinusoids, is responsible for the lipolysis of lipoproteins. Human HL contains four polymorphic sites: G-250A, T-710C, A-763G, and C-514T single-nucleotide polymorphism (SNPs). The last polymorphism is the focus of the current study. The genotypes associated with the C-514T polymorphism are CC (normal homozygous - W), CT (heterozygous - H), and TT (minor-allele homozygous - M). HL activity is significantly impaired in individuals of the TT and CT genotypes. A total of 58 post-menopausal women were studied. The subjects were hysterectomized women receiving hormone replacement therapy consisting of 0.625 mg of conjugated equine estrogen once a day. The inclusion criteria were menopause of up to three years and normal blood tests, radiographs, cervical-vaginal cytology, and densitometry. DNA was extracted from the buccal and blood cells of all 58 patients using a commercially available kit (GFX® - Amersham-Pharmacia, USA). Statistically significant reductions in triglycerides (t = 2.16; n = 58; p = 0.03) but not in total cholesterol (t = 0.14; n = 58; p = 0.89) were found after treatment. This group of good responders were carriers of the T allele; the CT and TT genotypes were present significantly more frequently than in the group of non-responders (p = 0.02 or p = 0.07, respectively). However, no significant difference in HDL-C (t = 0.94; n = 58; p = 0.35) or LDL-C (t = -0.83; n = 58; p = 0.41) was found in these patients. The variation in lipid profile associated with the C-514T polymorphism is significant, and the T allele is associated with the best response to ERT.
    Full-text · Article · Nov 2011 · Lipids in Health and Disease
Show more