SATgenε dietary strategy to investigate the impact of the apo E genotype on LDL-cholesterol response to dietary fat manipulation

Apolipoprotein E genotypes were measured in 83 patients with familial hypercholesterolaemia (FH) and in 175 blood donor controls. Following DNA extraction from peripheral blood, each sample was genotyped for the Apo E polymorphism by polymerase chain reaction. No significant differences were found in the levels of the ε2 and ε3 alleles between the two groups, while the ε4 allele was approximately twice as prevalent in the FH patients as in controls ( P = 0·006, df = 1). Of the FH patients, 8·4% were homozygous for the ε4 allele while this genotype was rare in controls ( P = 0·009, df = 1). These results suggest that the ε4 allele is over represented in the FH population and may contribute to increased cholesterol levels and consequent vascular disease.

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Genetic and Environmental Risk Factors for Intracerebral Hemorrhage

Stroke ◽

10.1161/str.32.suppl_1.321 ◽

2001 ◽

Vol 32 (suppl_1) ◽

pp. 321-321

Author(s):

Daniel Woo ◽

Laura Sauerbeck ◽

Brett M Kissela ◽

Jane C Khoury ◽

Rakesh Shukla ◽

...

Keyword(s):

Risk Factors ◽

Intracerebral Hemorrhage ◽

Environmental Risk ◽

Multivariable Analysis ◽

Population Based ◽

Environmental Risk Factors ◽

Degree Relative ◽

Increased Risk ◽

Apo E ◽

Apo E Genotype

27 Introduction: We report a planned midpoint analysis of a prospective, population-based, case-control study of the genetic and environmental risk factors of spontaneous, non-traumatic, intracerebral hemorrhage (ICH). Methods: Cases were matched to two controls by age, race and gender. Data was obtained by direct interview and review of all available medical and neuroimaging data. Apolipoprotein E (Apo E)genotype was determined by polymerase chain reaction. Multivariable analyses were performed using logistic regression modeling. Results: Between 6/97 and 2/00, 189 cases of ICH (150 white/39 black; 68 lobar/121 non-lobar) and 368 controls were enrolled into the study. Independent risk factors for multivariable analysis are listed in the table. Only prior stroke was an independent risk factor for both lobar and non-lobar ICH. Conclusions: The importance of individual genetic and environmental risk factors for ICH vary substantially by location of ICH. A history of a first-degree relative with ICH was associated with an increased risk of lobar ICH, independent of Apo E genotype. This finding indicates that other genetic risk factors may be important in the development of ICH.

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Apolipoprotein E, Cognitive Function, and Dementia in a General Population Aged 85 Years and Over

International Psychogeriatrics ◽

10.1017/s1041610200006487 ◽

2000 ◽

Vol 12 (3) ◽

pp. 379-387 ◽

Cited By ~ 15

Author(s):

Kati Juva ◽

Auli Verkkoniemi ◽

Petteri Viramo ◽

Tuomo Polvikoski ◽

Katariina Kainulainen ◽

...

Keyword(s):

Mini Mental State Examination ◽

Mmse Score ◽

Reference Population ◽

Apo E ◽

Diagnosis Of Dementia ◽

Ε4 Allele ◽

Very Old Age ◽

The Mean ◽

Apo E Genotype ◽

State Examination

We examined 510 subjects representing 83.2% of all citizens of a Finnish city aged 85 years or over. Mini-Mental State Examination (MMSE) scores, diagnosis of dementia by DSM-III-R criteria, and Apo-E genotype were determined. The prevalence of dementia was 38.6%. The odds ratio (OR) of the Apo-E ε4 carriers (with the reference population of people with the genotype ε3/ε3) for dementia was 2.36 (95% CI 1.58–3.58). There was a significant sex difference: The OR in women was 3.23 (95% CI 2.02–5.17) whereas among men it was insignificant. The mean MMSE score (± SD) among the Apo-E ε4 carriers (15.0 ± 10.0) and noncarriers (18.7 ± 8.6) (p < .001) differed among the whole population, but not within the demented or nondemented subjects analyzed separately. This study does not support the hypothesis that the Apo-E ε4 allele impairs cognitive functions of nondemented elderly, at least in those surviving to very old age.

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A gene-diet interaction-based score predicts response to dietary fat in the Women's Health Initiative

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa037 ◽

2020 ◽

Vol 111 (4) ◽

pp. 893-902

Author(s):

Kenneth Westerman ◽

Qing Liu ◽

Simin Liu ◽

Laurence D Parnell ◽

Paola Sebastiani ◽

...

Keyword(s):

Women's Health ◽

Dietary Fat ◽

Genetic Risk ◽

Ldl Cholesterol ◽

Response Prediction ◽

Women's Health Initiative ◽

Health Initiative ◽

Genome Wide ◽

Main Effect ◽

The Women’S Health Initiative

ABSTRACT Background Although diet response prediction for cardiometabolic risk factors (CRFs) has been demonstrated using single genetic variants and main-effect genetic risk scores, little investigation has gone into the development of genome-wide diet response scores. Objective We sought to leverage the multistudy setup of the Women's Health Initiative cohort to generate and test genetic scores for the response of 6 CRFs (BMI, systolic blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, and fasting glucose) to dietary fat. Methods A genome-wide interaction study was undertaken for each CRF in women (n ∼ 9000) not participating in the dietary modification (DM) trial, which focused on the reduction of dietary fat. Genetic scores based on these analyses were developed using a pruning-and-thresholding approach and tested for the prediction of 1-y CRF changes as well as long-term chronic disease development in DM trial participants (n ∼ 5000). Results Only 1 of these genetic scores, for LDL cholesterol, predicted changes in the associated CRF. This 1760-variant score explained 3.7% (95% CI: 0.09, 11.9) of the variance in 1-y LDL cholesterol changes in the intervention arm but was unassociated with changes in the control arm. In contrast, a main-effect genetic risk score for LDL cholesterol was not useful for predicting dietary fat response. Further investigation of this score with respect to downstream disease outcomes revealed suggestive differential associations across DM trial arms, especially with respect to coronary heart disease and stroke subtypes. Conclusions These results lay the foundation for the combination of many genome-wide gene-diet interactions for diet response prediction while highlighting the need for further research and larger samples in order to achieve robust biomarkers for use in personalized nutrition.

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Hypertriglyceridemia and Lower LDL Cholesterol Concentration in Relation to Apolipoprotein E Phenotypes in Myotonic Dystrophy

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100028675 ◽

1989 ◽

Vol 16 (1) ◽

pp. 129-133 ◽

Cited By ~ 8

Author(s):

Sital Moorjani ◽

Daniel Gaudet ◽

Claude Laberge ◽

Marie Christine Thibault ◽

Jean Mathieu ◽

...

Keyword(s):

Myotonic Dystrophy ◽

Ldl Cholesterol ◽

Plasma Cholesterol ◽

Plasma Lipid ◽

Cholesterol Concentration ◽

Plasma Triglycerides ◽

Ldl Particles ◽

Vldl Cholesterol ◽

Apo E

ABSTRACT:Plasma lipid, lipoprotein levels and apolipoprotein apo E phenotypes were determined in 70 patients with myotonic dystrophy (MyD) and 81 controls. Marked differences were noticed in the apo E phenotype frequencies between the two groups. Plasma triglycerides and VLDL cholesterol were higher in MyD than controls, but only the latter was related to differences in the apo E phenotypes between two groups. Accordingly, the ratio of VLDL cholesterol/plasma triglycerides was increased significantly in MyD, suggesting accumulation of intermediary density particles due to lower affinity of E2 containing lipoproteins for lipoprotein cell receptors. The LDL cholesterol concentration was lower in MyD than controls and was related to differences in the apo E phenotype frequencies between the two groups. These results indicate increased removal of LDL particles in the apo E2 phenotypes, perhaps due to upregulation of LDL (B, E) receptor activity. Plasma cholesterol and HDL cholesterol concentrations were similar in both groups. Another feature of the study was lower levels of plasma cholesterol, triglycerides, VLDL and LDL cholesterol in the homozygous E4:E4 phenotype. These results suggest increased clearance rate of both VLDL and LDL particles and support the concept that apo E4-containing lipoproteins have higher in vivo affinity for ape E and/or B, E receptors.

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SAT-576 Possible Involvement of Thyroid Function in PCSK9 Inhibitor Therapy

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.477 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Masayasu Iwabuchi

Keyword(s):

Thyroid Function ◽

Ldl Cholesterol ◽

Inhibitor Therapy ◽

Thyroid Peroxidase ◽

Thyroid Function Tests ◽

Pcsk9 Inhibitors ◽

Free T4 ◽

Hyperthyroid Patient ◽

Pcsk9 Inhibitor ◽

The Impact

Abstract INTRODUCTION Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibition is an effective strategy for lowering plasma LDL-cholesterol and enhancing the LDL-cholesterol lowering ability of statins. PCSK9, a serine protease that binds to the LDL receptor promoting its degradation, is an important regulator of LDL metabolism. In addition, LDL-cholesterol is also controlled by TSH and thyroid hormones via PCSK9. TSH has received increasing attention as being closely associated with increased LDL-cholesterol level and higher atherosclerotic risks. In vitro study, the effects of TSH on hepatic PCSK9 expression in HepG2 cells were reported (1). I here report a case of transient hyperthyroidism secondary to PCSK9 inhibitor therapy. This case highlights the involvement of thyroid function in PCSK9 Inhibitor therapy. CLINICAL CASE A 65-year-old man had a weight loss of 6 kg (13 lbs.) in 4 months, accompanied with fatigue. He had a past history of myocardial infarction and his LDL was 83 mg/dL by 2.5mg of rosuvastatin and heart rate was controlled by 10mg of carvedilol. Six months ago, he started a PCSK9 Inhibitor therapy with 140mg of evolocumab every 2 weeks for 6 weeks. He had no preceding viral illness and denied anterior neck pain or tenderness. His height was 1.53 m, weight 52.6 kg (115 lbs.), and body mass index (BMI) 22.46 kg/m2. His thyroid was not enlarged and non-tender without clear palpable thyroid nodules or neck lymph nodes. Hyperthyroidism was suspected and confirmed by thyroid function tests: TSH was less than 0.0005 μIU/mL (normal 0.35–4.94), and free T4 1.830 ng/dL (0.70–1.48). Graves’ disease was considered, and thyroid antibody tests performed. Thyroid peroxidase (TPO) antibody titer was less than 9 IU/mL (<9), and TSI 141% (<120%). To confirm the diagnosis of this hyperthyroid patient, Technetium-99m uptake and scan was done which showed uptake of 0.8% (0.5–7%). After careful observation for 2 months with 5mg of carvedilol, he turned asymptomatic and free T4 lowered to 1.480 ng/dL and TSH remained less than 0.0005 μIU/mL. CLINICAL LESSONS I here report a case of transient hyperthyroidism secondary to PCSK9 inhibitor therapy. There has been no report of hyperthyroidism induced by PCSK9 inhibitors. Immunological influence of anti-PCSK9 therapy on thyroid is unknown. In this case, the decrease of TSH due to hyperthyroidism was considered to reduce hepatic PCSK9 expression, leading to additive effect to PCSK9 inhibitor. PCSK9 inhibitors may modify the effects of hyperlipidemia treatment by causing changes in thyroid function. When using PCSK9 inhibitors, follow-up of thyroid function should be considered. This case highlights the involvement of thyroid function in PCSK9 inhibitor therapy. Reference (1) Gong, Y., Ma, Y., et al. Thyroid stimulating hormone exhibits the impact on LDLR/LDL-c via up-regulating hepatic PCSK9 expression. Metabolism. 2017;76;32–41

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The impact of hypertriglyceridaemia on LDL cholesterol in diabetics

Atherosclerosis ◽

10.1016/s0021-9150(99)80725-4 ◽

1999 ◽

Vol 144 ◽

pp. 190

Author(s):

L.M. Loh ◽

E.S. Tai ◽

B.S. Chew ◽

A.H.C. Kua ◽

A.C.K. Fok ◽

...

Keyword(s):

Ldl Cholesterol ◽

The Impact

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LDL-Cholesterol Lowering of Plant Sterols and Stanols—Which Factors Influence Their Efficacy?

Nutrients ◽

10.3390/nu10091262 ◽

2018 ◽

Vol 10 (9) ◽

pp. 1262 ◽

Cited By ~ 20

Author(s):

Elke Trautwein ◽

Mario Vermeer ◽

Harry Hiemstra ◽

Rouyanne Ras

Keyword(s):

Ldl Cholesterol ◽

Critical Factor ◽

Time Of Day ◽

Plant Sterols ◽

Food Supplements ◽

Lowering Effect ◽

Daily Intakes ◽

Meta Analyses ◽

Main Meal ◽

The Impact

The LDL-cholesterol (LDL-C) lowering effect of plant sterols/stanols (PSS) is summarized in several meta-analyses showing a dose-response relationship with intakes of 1.5 to 3 g/day lowering LDL-C by 7.5% to 12%. This review summarizes evidence for the impact of various factors potentially influencing the LDL-C-lowering efficacy of PSS. PSS are efficacious in all food formats and in food supplements. Some factors related to food format, e.g., solid vs. liquid foods, seem to impact efficacy, while there is no difference between free PSS and esters. Compared to multiple daily intakes, once-a-day intake of PSS, especially in the morning with light breakfast, leads to a sub-optimal LDL-C lowering. However, intake frequency seems influenced by intake occasion, i.e., with or without a meal, and time of day. Meal intake is a critical factor for an optimal LDL-C lowering efficacy of PSS. While age has no impact, gender is suggested to influence the LDL-C lowering effect of PSS with greater reductions reported for men than women; but overall evidence is inconclusive and larger studies show no gender by treatment interaction. In conclusion, PSS are efficacious in all foods and food supplements; for optimal efficacy they should be consumed with a (main) meal and twice daily.

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