Study Into Genetic Influence on Cholesterol Response to Dietary Fat

Apolipoprotein E Genotype as a Determinant of LDL-cholesterol Response to Dietary Fat Manipulation

Cardiovascular disease (CVD) is recognised as one of the main causes of death in the western world. LDL- cholesterol ('bad' cholesterol) and other lipids (fats) are important CVD risk factors. Apolipoprotein E (apoE) is an important transporter of fats in the blood. ApoE comes in E2, E3 and E4 forms, depending on your genetic make up. Approximately 60% of the UK population are E3/E3, 25% E4 carriers and 15% E2 carriers. There is some evidence to suggest that an E4 genotype may put you at modestly higher risk of CVD. Furthermore although very inconclusive previous studies have suggested that E4 individuals are slightly more sensitive to the LDL-cholesterol modifying effects of dietary fats (saturated fat, total fat, fish oil) showing slightly, greater reductions when low levels of these fat are consumed, and greater increases when high levels of these fat are consumed. Therefore, the aims of the Satgene study is to examine the impact of modifications in dietary total fat and saturated fat intakes, alone and in combination with fish oil supplement on LDL-cholesterol and other blood lipids, in individuals with an E3 and E4 genotype. The levels of total fat and saturated fat used in the current study are within the range observed in a typical UK population.

Inclusion Criteria:

Men & women 35-70 years BMI 20-32 kg/m2 Haemoglobin (anaemia): 12.5-18.0g/l (men) and > 11.5-16g/l (women) Gamma GT (liver function) (< 80 IU/l), Triglyceride (between 1-4 mmol/l), Plasma total cholesterol (4.5-8 mmol/l) Glucose (World Health organisation recommend <7 mmol/L).

Exclusion Criteria:

• Females who are breast feeding, may be pregnant, or if child-bearing potential are not taking effective contraceptive precautions
• Likely to alter oral contraceptive or HRT usage during the course of the study
• Blood Pressure > 160/100 mm Hg (UK guidelines for stage 2 hypertension)
• Had suffered a myocardial infarction or stroke in the previous 12 months
• Hypertensive medication
• Diabetics type I and II
• Any volunteers on a weight reducing diet, or vegan/vegetarians as study requires consumption of dairy products and fish oils
• On high dose fish oil supplements (> 1g EPA + DHA per day)
• Elevated lipids requiring medication such as statins, fibrates, gall bladder problems or other abnormalities of fat metabolism
• Subjects not willing to make the necessary dietary changes during the study
• Subjects drinking excessive alcohol (UK recommendations/wk currently for men are, no more than 21 units of alcohol per week or more than four units in any one day. For women, no more than 14 units of alcohol per week or more than three units per day).
• Subjects who train at a high level, or attend more than 3 hours organised exercise classes per week