Evaluation of beef eating quality by Irish consumers.

A consumer's decision to purchase beef is strongly linked to its sensory properties and consistent eating quality is one of the most important attributes. Consumer taste panels were held according to the Meat Standards Australia guidelines and consumers scored beef according to its palatability attributes and completed a socio-demographic questionnaire. Consumers were able to distinguish between beef quality on a scale from unsatisfactory to premium with high accuracy. Premium cuts of beef scored significantly higher on all of the scales compared to poorer quality cuts. Men rated grilled beef higher on juiciness and flavour scales compared to women. Being the main purchaser of beef had no impact on rating scores. Overall the results show that consumers can judge eating quality with high accuracy. Further research is needed to determine how best to communicate inherent benefits that are not visible into extrinsic eating quality indicators, to provide the consumer with consistent indications of quality at the point of purchase.

An examination of the influence of eating location on the diets of Irish children.

OBJECTIVES: To examine the influence of eating location on the quality of the diets of Irish children and to compare intakes at home with intakes at other people's homes and intakes outside the home, and to compare intakes at various locations outside the home. DESIGN: Food intake was measured using a 7-day weighed diary in 594 children from the Republic of Ireland (aged 5-12 years). Details of where the food was prepared or obtained were also recorded. RESULTS: Eighty-nine per cent of all eating occasions occurred at home; < 6% occurred at both other people's homes and outside the home (takeaway, restaurant, shop, other). The percentage of food energy from fat was above the recommended 35% at other people's homes and outside the home, specifically at takeaways and restaurants. Fibre and micronutrient intakes (per 10 MJ) were significantly higher at home than at the other locations (P < 0.05). Within the 'out' locations, fibre and micronutrient intakes were generally higher at restaurants and lower at shops. High consumers of foods outside the home had a statistically significant, but relatively small decline in nutrient intakes compared with non- or low consumers. Chips and processed potatoes, meat products, savouries, sugars and confectionery, and savoury snacks made the greatest contribution to foods consumed outside the home. CONCLUSIONS: The main focus of nutrition policies to improve the diets of Irish children should be the home environment rather than the food service sector. However, guidelines could call for better food choices outside the home to improve nutrient intakes.

Relationship between attitudes towards healthy eating and dietary behaviour, lifestyle and demographic factors in a representative sample of Irish adults.

Attitudes towards healthy eating were explored according to dietary, lifestyle and socio-demographic correlates in a random sample of 1256 Irish adults. Data were obtained from an Irish cross-sectional survey (1997-1999). A self-administered questionnaire was used to obtain attitudinal information. Food consumption was estimated using a 7-d food diary. A majority of the sample had a positive attitude or motivation towards their healthy eating behaviour. Those who perceived their own eating habits to be healthy were more likely to comply with current dietary guidelines than those who did not. Females, increasing age, higher social class, tertiary education, non-smokers, lower body-weights and increased recreational activity were associated with a lower odds ratio (OR) for having a negative attitude towards their healthy eating behaviour. An increased intake (g/d) of breakfast cereals, vegetables, fruit and poultry dishes were associated with decreased OR for negative attitudes towards their healthy eating behaviour, while an increased intake of high-calorie beverages (g/d) was associated with an increased OR. It can be concluded that attitudes or motivation towards eating healthily was related to measured dietary and lifestyle behaviour in this sample. Future research is warranted to devise appropriate methods of instituting attitude change towards dietary behaviour in certain subgroups of the population.

Prevalence of overweight and obesity in Irish school children, using four different definitions.

OBJECTIVE: To determine the prevalence of overweight and obesity in Irish children using four different weight-for-height methods and to examine secular trends from previous national data. DESIGN: A cross-sectional survey. Weight and height were measured according to standard procedures and used to determine the prevalence of overweight and obesity using four weight-for-height methods of assessment, actual relative weight, the Centers for Disease Control and Prevention body mass index (BMI) for age charts for boys and girls, the BMI reference curves for the UK 1990 and the International Obesity Task Force age- and sex-specific BMI cutoffs. SETTING: The survey was carried out between 2003 and 2004 in the Republic of Ireland. SUBJECTS: Random representative sample of 596 children aged 5-12 years. RESULTS: The prevalence of overweight and obesity in Irish children is high, but varies considerably with each method. The prevalence of obesity in boys ranged from 4.1 to 11.2 % and in girls from 9.3 to 16.3%. Between 1990 and 2005, depending on the method used, there was a two-to-fourfold increase in obesity in children aged 8-12 years. CONCLUSION: It is evident given the variation displayed in the prevalence of obesity when using the different methods, that there is a discernible need for a single definition to identify the obese child in Ireland. The findings show a high prevalence of overweight and obesity in Irish school children and the increase in the prevalence of obesity over the last 15 years highlights this growing public health issue.

Associations between daily food intake and excess adiposity in Irish adults: towards the development of food-based dietary guidelines for reducing the prevalence of overweight and obesity.

BACKGROUND: The prevalence of obesity has nearly doubled in Ireland since 1990 and over half of the population has a large waist circumference (WC). No food-based, dietary guidelines exist in Ireland for a reduction in the prevalence of body fat or obesity. OBJECTIVE: To examine the association between daily food intake and categories of body mass index and WC for the development of dietary guidelines to combat obesity. DESIGN: Cross-sectional study of a random representative sample of 1379 adults aged 18-64 years from Northern Ireland and the Republic of Ireland. MEASUREMENTS: Weight, height and WC were measured according to standard procedures. Diet was assessed using a 7-day food diary from which 28 food groups were generated and entered into logistic regression analysis. RESULTS: Higher mean daily consumption of most of the 28 food groups was associated with an increased likelihood of being classified as obese or at waist action level 2, compared to normal weight and normal WC. The strongest associations were found for savoury snacks, butter and full fat spreads. Contrary to popular opinion, not one individual food group but rather a combination of many foods was associated with excess adiposity. CONCLUSIONS: Body mass index and WC in adults are strongly influenced by the amount of food consumed. Public health policies for a reduction in body fat and obesity may be more effective if the emphasis is placed on a reduction of food and beverages consumed as opposed to the traditional dietary recommendations for macronutrients.

The influence of cereal and dairy consumption on the Irish diet: implications for developing food-based dietary guidelines.

OBJECTIVES: To estimate the intakes of cereal and dairy products and their contribution to nutrient intakes in men and women from the Republic of Ireland with a view to formulating food-based dietary guidelines. DESIGN: The North/South Ireland Food Consumption Survey established a database of habitual food and drink consumption using a 7-day food diary. From this database all cereal and dairy products from recipes and identifiable sources were identified and a new database was generated from which analysis of the role of cereal and dairy products in the diet was carried out. RESULTS: Almost 100% of the population consumed cereal and dairy products over the course of the survey week. In general, men consumed significantly more cereal and dairy products than did women (P<0.05). Cereal products made an important contribution to the mean daily intakes of energy (26%), protein (21%), fat (13%), carbohydrate (41%), fibre (45%), iron (43%) and folate (27%). Dairy products also contributed largely to the mean daily intakes of energy (11%), protein (14%), fat (17%), calcium (48%), phosphorus (24%) and vitamin A (27%). Analysis of nutrient intakes across tertiles of cereal and dairy consumption showed that high consumers of wholemeal bread, breakfast cereals, reduced-fat milk and yoghurt had lower fat and higher carbohydrate, fibre and micronutrient intakes than low consumers of these foods. CONCLUSIONS: Findings from the present study could be used to develop effective health strategies to implement changes in cereal and dairy consumption that could alter fat, fibre and micronutrient intakes in the diet.

The temporal pattern of the contribution of fat to energy and of food groups to fat at various eating locations: implications for developing food-based dietary guidelines.

OBJECTIVES: To examine the temporal pattern of the number of eating occasions that occurred at home, at work and outside the home, and to examine the contribution of fat to energy and the contribution of 26 food groups to fat at home and outside the home. DESIGN AND SETTING: Food intake data were collected using a 7-day food diary from a random sample of 18-64-year-old adults from the Republic of Ireland (n=958). Respondents recorded the day, time and location of every eating occasion. RESULTS: The number of eating occasions was constant across the days of the week for meals consumed at home, whereas the number of eating occasions increased at weekends for meals outside the home. The contribution of fat to energy approximated the 35% recommendation at home from Monday to Friday, but increased above this on Saturday and Sunday. The contribution of fat to energy outside the home was always above the recommendation. The food groups that contributed most to fat were similar at home and outside the home. These included butter and full-fat spreads, fresh meat, meat products, meat dishes, biscuits, cakes and pastries, whole milk, and chips and processed potatoes. CONCLUSION: The contribution of fat to energy was above the recommendations when eating outside the home, regardless of day of the week. A number of food groups have been identified that contributed most to fat intake outside the home and these might be targeted in developing public health nutrition strategies to reduce fat intake.

The influence of eating location on nutrient intakes in Irish adults: implications for developing food-based dietary guidelines.

OBJECTIVES: To examine the contribution of the food service sector to the nutrient quality of the Irish diet, and to compare intakes at home, work and outside the home ('out') and within the subgroups of the out location (pub, deli, takeaway). DESIGN AND SETTING: Random sample of adults from the Republic of Ireland. Food intake data were collected using a 7-day food diary. Respondents recorded the location of every eating occasion determined by where the food was prepared rather than consumed. RESULTS: Intakes of energy, protein, fat and carbohydrate were significantly greater at home than at work or out (P<0.05). The intake of alcohol was significantly (P<0.001) greater out than at home or work. The percentage contribution of fat to energy was above the recommendations (33% of total energy and 35% of food energy) for both men and women at all locations, with the exception of the contribution of fat to total energy for men at the out location. Within the subgroups of the out location, the contribution of alcohol to total energy was greatest in pubs and the contribution of fat to both total and food energy was greatest in takeaways. Intakes of fibre and most micronutrients per 10 MJ of food energy were greater (P<0.05) at home than at work or out. CONCLUSION: Foods eaten outside the home contribute a disproportionately high level of fat intake and should be targeted in public health nutrition strategies.

Analysis of the temporal intake of cereal and dairy products in Irish adults: implications for developing food-based dietary guidelines.

OBJECTIVES: To analyse the temporal distribution of the intake of cereal and dairy products in the Republic of Ireland. DESIGN: The North/South Ireland Food Consumption Survey established a database of habitual food and drink consumption using a 7-day food diary. The database also recorded the time and day of food consumption. Mean intakes of cereal and dairy products were calculated for time of the day and day of the week. RESULTS: At the weekend, the percentage of consumers decreased for nearly all cereal and dairy products. White bread, total cereals, full-fat milk and total dairy intakes were significantly lower at the weekend (P<0.01) compared with weekdays. Intakes of cereal and dairy products over time of the day showed clear mealtime or snacking patterns when the number of consumers was controlled for. White bread, wholemeal bread, total cereals, full-fat milk, reduced-fat milk and total dairy intakes showed mealtime peaks for morning, afternoon and evening. When examined by tertile of intake, tertile of percentage energy from fat and tertile of fibre intake, intakes of cereal and dairy products over time of the day and day of the week were similar to trends described above, regardless of the tertile. CONCLUSIONS: Temporal analysis of the intakes of cereal and dairy products did not reveal any unusual trends in this population. However, the significant methodological issues raised in this paper will be of benefit to other aspects of research in this area.

Overweight, obesity and physical activity levels in Irish adults: evidence from the North/South Ireland food consumption survey.

In the present paper the prevalence of obesity (BMI > or = 30 kg/m2) and current physical activity levels in Irish adults have been evaluated. The prevalence of obesity in Irish adults is currently 18%, with men at 20% and women at 16%. A further 47% of men and 33% of women are overweight (BMI 25.0-29.9 kg/m2). Since 1990, obesity has more than doubled in men from 8% to 20%, and increased from 13% to 16% in women. The highest prevalence of obesity (30%) was found in women aged 51-64years. Defined waist circumference action levels identified 48% of the population who are in need of weight management and who also are at a 1.5-4.5 times increased risk of having at least one cardiovascular disease risk factor. Physical activity levels were low overall. Men were more active in work and recreational pursuits than women, but women were more active in household activities. Walking was the most popular recreational pursuit. However, TV viewing occupied most of the leisure time of men and women. Higher levels of activity were associated with a lower BMI and waist circumference. The results indicate the need for sensitive and individualised strategies to promote physical activity and to achieve a healthy weight status.

Susceptibility of LDL to oxidative modification in healthy volunteers supplemented with low doses of n-3 polyunsaturated fatty acids.

The objective of the present study was to evaluate the oxidative susceptibility of LDL in human volunteers following supplementation with various low doses (<1 g/d) of n-3 polyunsaturated fatty acids (PUFA). Sixty-two healthy volunteers (thirty-seven males and twenty-five females, aged 19-63 years) were recruited to take part in a randomised placebo-controlled trial. Volunteers were required to take 0.9, 0.6 or 0.3 g n-3 PUFA as fish oil or placebo capsules daily for 16 weeks. Susceptibility of LDL to oxidative modification was assessed by measuring the production of conjugated dienes and thiobarbituric acid-reactive substances in LDL oxidised by Cu2+ (15 microM) or 2,2'-azobis(2-amidinopropane) dihydrochloride (1 mM) for 5 h. Plasma fatty acid and LDL-fatty acid composition, cholesterol levels and antioxidant concentrations were also measured. While post-treatment n-3 PUFA compositions of plasma and LDL reflected the capsule contents, no meaningful differences in antioxidant concentrations or cholesterol levels were observed between the groups. Supplementation with low doses of n-3 PUFA as fish oil did not influence the oxidative susceptibility of LDL. The results of the present study suggest that moderate dietary intakes of n-3 PUFA do not significantly influence the susceptibility of LDL to oxidative modification in vitro.

Analyses of the anthropometric data from the North/South Ireland Food Consumption Survey.

OBJECTIVE: To obtain measured anthropometric data for weight, height and other parameters not previously measured in the Irish population such as waist and hip circumferences and body composition. DESIGN: A cross-sectional survey. Weight, height, waist circumference, hip circumference and body composition were measured according to standard procedures. SETTING: Northern Ireland and the Republic of Ireland, 1997-1999. SUBJECTS: Random representative sample of 1379 adults aged 18-64 years. RESULTS: With the exception of body fat, all anthropometric values were significantly higher for men than women (P<0.001). All measurements were significantly higher in the 36-50-year-old age group compared with 18-35 year olds. Height was the exception, which decreased significantly with age (P<0.05). Weight, height and body mass index (BMI) have increased in Ireland since last measured in 1988 and in 1990. Over the last decade, obesity has increased in men 2.5 fold from 8% to 20% and in women by 1.25 fold from 13% to 16%. Significantly more women have a normal BMI than men (50.4% vs. 33.3%; P<0.05). Cut-off points for a high waist circumference and high waist-to-hip ratio identified 47% and 33% of the population, respectively, to be at an increased risk for cardiovascular disease. Social class did not have any significant effect on mean BMI. Location of residence influenced BMI but not in any consistent manner. Ex-smokers had a significantly higher BMI than non-smokers and smokers (P<0.05). CONCLUSIONS: A revision of current recommendations for combating obesity is warranted to improve the health of the Irish population. Further research is needed to identify the factors that have contributed to the dramatic increase in the prevalence of obesity in men over the last decade and have resulted in a higher prevalence of obesity in men than in women.

Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults.

In hypercholesterolemic rabbits, oral L-arginine (the substrate for endothelium derived nitric oxide) attenuates endothelial dysfunction and atheroma formation, but the effect in hypercholesterolemic humans is unknown. Using high resolution external ultrasound, we studied arterial physiology in 27 hypercholesterolemic subjects aged 29+/-5 (19-40) years, with known endothelial dysfunction and LDL-cholesterol levels of 238+/-43 mg/dl. Each subject was studied before and after 4 wk of L-arginine (7 grams x 3/day) or placebo powder, with 4 wk washout, in a randomized double-blind crossover study. Brachial artery diameter was measured at rest, during increased flow (causing endothelium-dependent dilation, EDD) and after sublingual glyceryl trinitrate (causing endothelium-independent dilation). After oral L-arginine, plasma L-arginine levels rose from 115+/-103 to 231+/-125 micromol/liter (P<0.001), and EDD improved from 1.7+/-1.3 to 5.6+/-3.0% (P<0.001). In contrast there was no significant change in response to glyceryl trinitrate. After placebo there were no changes in endothelium-dependent or independent vascular responses. Lipid levels were unchanged after L-arginine and placebo. Dietary supplementation with L-arginine significantly improves EDD in hypercholesterolemic young adults, and this may impact favorably on the atherogenic process.

Characterization of mutations in the low density lipoprotein (LDL)-receptor gene in patients with homozygous familial hypercholesterolemia, and frequency of these mutations in FH patients in the United Kingdom.

Mutations in the gene for the low density lipoprotein (LDL) receptor have been identified in 15 patients with homozygous familial hypercholesterolemia (FH). Five patients are homozygous at the LDL-receptor locus; their mutant alleles include Glu387Lys and Pro664Leu in patients of Asian-Indian descent, Cys292Stop in a Greek Cypriot, Cys281Trp in a Turkish patient, and Gln 540Stop in a West Indian. The other 10 patients (9 of apparently British ancestry) are compound heterozygotes. Mutations have been identified in 18 of 20 possible alleles, including Glu80Lys (2 patients), Pro664Leu (3 patients), Asp69Gly, Cys176Arg, Cys227Tyr, Ser265Arg, Asp280Ala, Asp283Glu, Arg329Pro, Asp461Asn, Leu578Ser, a single bp deletion in exon 15, a 21 bp duplication of codons 200-206 and two large deletions. The seven mutations underlined above have not been described previously. The two uncharacterized mutant alleles fail to produce detectable amounts of mRNA. LDL-receptor activity in cultured cells from 13 of the 15 homozygous patients varied from undetectable to about 30% of normal, but there was no correlation between LDL-receptor activity and the untreated plasma cholesterol concentration in these patients. When genomic DNA from 295 patients with a clinical diagnosis of FH was screened for 29 mutations found in these and other FH patients of British ancestry, most were identified in only one or a few individuals. Four patients heterozygous for the Asp461Asn allele showed a wide range of clinical manifestations. These observations confirm the striking heterogeneity underlying FH in most populations and demonstrate the variability in phenotype between patients with the same mutation.

Hyperlipidaemia does not impair vascular endothelial function in glycogen storage disease type 1a.

Patients with glycogen storage disease type 1 (GSD-1) often have marked hyperlipidaemia with abnormal lipoprotein profiles. This metabolic abnormality improves, but is not fully corrected, with dietary therapy and therefore these patients may be at high risk for the development of atherosclerosis. Endothelial dysfunction is an early event in atherogenesis and can be detected in children and young adults at high risk. We studied endothelial function, using a non-invasive ultrasonographic method, in the brachial arteries of 6 adult GSD-1a patients (aged 23-33 years) with mean cholesterol of 7.9 mmol/l (range 4.7 to 14.6) and mean triglycerides of 9.1 mmol/l (range 4.1 to 21.3), and 12 age- and sex-matched normolipidaemic controls. Flow-mediated (endothelium-dependent) dilation was similar in patients and controls (8.2% vs. 10.5%; P = 0.20). Although the patient numbers are small, these results are consistent with the surprising lack of clinically evident atherosclerosis in GSD-1. The reasons these patients appear less susceptible to the damaging arterial effects of hyperlipidaemia are unknown. These results may have implications for others with secondary hyperlipidaemias.

Use of the single-strand conformational polymorphism method to detect recurrent and novel mutations in the low-density lipoprotein receptor gene in patients with familial hypercholesterolaemia: detection of a novel mutation Asp200-->Gly.

The single-strand conformational polymorphism (SSCP) method was used to look for mutations in the 3' half of exon 4 of the low-density lipoprotein receptor gene in patients with familial hypercholesterolaemia (FH). One set of conditions were found which allowed the detection of four of the mutations that have previously been reported in this part of the gene and detected in patients in the United Kingdom: the 3-bp deletion (del Gly197) the 2-bp deletion (STOP 216), the Asp206-->Glu mutation and the Cys210-->STOP. The method was used to screen 50 patients with definite or probable FH from London. Two were identified who were carriers of the 3-bp deletion of Gly197, one who was a carrier of the Asp206-->Glu mutation and one who was a carrier of a novel mutation that alters Asp200-->Gly. This mutation creates a cutting site for the restriction enzyme MspI. In a further sample of 200 patients from London with FH one additional apparently unrelated individual was detected who was a carrier of this defect. Thus in the sample of 50 patients, four (8%) had a mutation in this part of exon 4 that could be readily detected using the SSCP method, suggesting that this approach will be useful for rapid screening for mutations in patients with FH.

Characterization of two new point mutations in the low density lipoprotein receptor genes of an English patient with homozygous familial hypercholesterolemia.

Two new point mutations have been detected in the low density lipoprotein (LDL) receptor gene of a patient with a clinical diagnosis of homozygous familial hypercholesterolemia (FH). The patient is a compound heterozygote, in whom the mutant allele inherited from his English father has a single base substitution of A for G in exon 3, changing the codon for residue 80 in the mature protein from glutamic acid to lysine. The mutant allele inherited from his mother, who is of Irish origin, has a single base pair deletion in the codon for residue 743 in exon 15 that causes a frameshift and introduces a new stop codon in the adjacent position. The glu80 to lys mutation results in a transport-defective phenotype and a mature protein that migrates abnormally slowly on nonreduced SDS-PAGE, but normally under reducing conditions; this was confirmed by site-directed mutagenesis and expression in vitro. The deletion in exon 15 results in a null phenotype in which the putative truncated receptor protein cannot be detected in cultured skin fibroblasts and the amount of mRNA derived from the allele is reduced. The glu80 to lys mutation was found in a further five unrelated individuals in a sample of 200 FH patients from the London area and in 11 from a sample of 77 FH patients from Manchester. Haplotype analysis suggested that all the patients had inherited this allele from a common ancestor. The deletion in exon 15 was not found in the London sample, nor in any unrelated individuals in the Manchester sample.

Blood rheology and fibrinogen in children with familial hypercholesterolaemia.

Whole blood and plasma viscosity, red cell aggregability and deformability, and plasma fibrinogen have been compared between 16 children aged between 6 and 18 years with heterozygous familial hypercholesterolaemia (FH) and 16 controls individually matched for age and sex. Mean (SD) plasma cholesterol was 7.19 (1.23) mmol/l in the patients and 4.31 (0.84) mmol/l in the controls. This was due to a similar difference in low density lipoprotein (LDL) cholesterol, while triglycerides and high density lipoprotein (HDL) cholesterol were similar between groups. No differences were seen in any of the rheological parameters between the two groups. This suggests that the rheological abnormalities seen in adults with FH are not a direct consequence of their hyperlipidaemia, and may instead be a reflection of their more extensive atherosclerosis.

Relationship between apolipoprotein(a) phenotype, lipoprotein(a) concentration in plasma, and low density lipoprotein receptor function in a large kindred with familial hypercholesterolemia due to the pro664----leu mutation in the LDL receptor gene.

In a large kindred of 66 individuals, 22 were identified as heterozygous and 3 as homozygous for a mutation (pro664----leu) in the LDL-receptor gene that gives rise to familial hypercholesterolaemia (FH). All the heterozygotes had a raised level of plasma total cholesterol and low density lipoprotein cholesterol, but were remarkably free from premature coronary disease. Determination of apolipoprotein(a) (apo(a)) phenotype and lipoprotein(a) (Lp(a)) concentration in plasma revealed that in many instances, involving individuals with various apo(a) phenotypes, there was no difference in plasma Lp(a) concentration between an FH heterozygote and an unaffected sibling with the same apo(a) phenotype. No significant difference in Lp(a) concentration was observed between groups of FH and non-FH of the same apo(a) phenotype, although in each case the mean value for the FH group was greater than that for the non-FH group. There was also evidence for an inherited trait that markedly increased Lp(a) concentration, which did not segregate with apo(a) phenotype or the defective LDL-receptor allele. The data provide no evidence for a strong multiplicative interaction between the gene loci for apo(a) and the LDL receptor.

Clinical signs of familial hypercholesterolemia in patients with familial defective apolipoprotein B-100 and normal low density lipoprotein receptor function.

In a previous study (Tybjaerg-Hansen et al, Atherosclerosis 1990;80:235-242), we identified nine patients heterozygous for the apolipoprotein B (apo B) arginine-to-glutamine (Arg3,500----Gln) mutation (familial defective apolipoprotein B-100 [FDB]). Six of these had been diagnosed clinically as familial hypercholesterolemic (FH) heterozygotes. We have since examined low density lipoprotein (LDL) receptor function in the FDB index patients and in three of their families. Skin fibroblasts from seven of seven unrelated FDB patients from whom cell lines were established exhibited normal high-affinity binding and degradation of normal LDL in vitro. In the three families, a raised plasma LDL concentration did not segregate with a haplotype of two polymorphic restriction sites at the LDL receptor locus. We conclude that the clinical and biochemical signs of classical FH can occur in the presence of the FDB mutation and a normal LDL receptor gene. In a four-generation family with 11 proven or presumed FDB heterozygotes, expression of the mutation ranged from normal plasma LDL concentrations and no clinical signs in two individuals, to hypercholesterolemia and death from myocardial infarction at age 31. Variable expression of the FDB mutation could not be explained conclusively by variation in diet, body mass index, smoking habit, apo E genotype, or plasma Lp(a) concentration.