The effect of diet on blood lipids has been under intensive study during recent decades. However, diet in the context of the hyperapobetalipoproteinemia (hyperapoB) phenotype has received less ...attention. The hyperapoB phenotype is commonly encountered in patients with premature coronary heart disease. It is defined as a combination of an increased concentration of apolipoprotein B (apo B), a normal concentration of LDL cholesterol (LDL-C), and as a result, a low LDL-C/apo B ratio. We studied the associations between diet and blood lipids in a cohort of 534 children and young adults 9 to 24 years old. The ratio of polyunsaturated to saturated fats (P/S ratio) correlated (r=-0.19, P<.001) with the LDL-C/apo B ratio. This association was also found when the model was adjusted with triglycerides (r=-0.24, P<.001). A change in the P/S ratio from 0.10 to 0.60 corresponded to a decrease of 0.12 in the LDL-C/apo B ratio, and in the highest apo B decile, the P/S value was higher in hyperapoB individuals (0.33) than in others (0.28, P=.019). Our results imply that the fatty acid composition of the diet may be one of the environmental factors that influence the hyperapoB phenotype expression.
Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain ~25% of the heritability of the phenotypes. To date, no unbiased screen ...for gene-environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79×10-9. There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus.
Background
Familial combined hyperlipidaemia (FCHL) is a common hereditary disorder. Hypertriglyceridaemia is associated with glucose intolerance and insulin resistance.
Methods
To study glucose ...tolerance in FCHL patients with different lipid phenotypes hypercholesterolaemia (IIA), mixed hyperlipidaemia (IIB), hypertriglyceridaemia (IV), we investigated 253 family members and 92 spouses arising from 33 well‐defined Finnish FCHL pedigrees.
Results
In oral glucose tolerance tests. the affected family members had higher values for glucose area under the curve than did non‐affected family members (673 ± 127 min mmol L−1, 754 ± 145 min mmol L−1, 846 ± 180 min mmol L−1 and 838 ± 183 min mmol L−1 for phenotypes normal, IIA, IIB and IV respectively; P < 0.001 after adjustment for body mass index, waist circumference and age). Impaired glucose tolerance and diabetes were more common among affected than non‐affected family members (prevalences of normal glucose tolerance 94.0%, 80.0%, 54.3% and 58.5% for phenotypes normal, IIA, IIB and IV).
Conclusion
Affected FCHL family members were more glucose intolerant than non‐affected family members. In men, this disturbance was not related to lipid phenotype nor was it explained by obesity.
Objective: To assess nutrient intakes relevant in the prevention of cardiovascular diseases (CVD) among young adults in Finland and to find past and present determinants of quality of diet. Design: ...Prospective study, 21 years of follow-up. Setting: The Cardiovascular Risk in Young Finns Study, Finland. Subjects: At baseline in 1980: 3569 children aged 3-18 y participated (83% of those invited), and every second of them (1780) were selected to the dietary study. At follow-ups in 1986 and 2001: 1200 and 1037 of the original sample, respectively, participated. Methods: Food consumption was assessed using 48-h dietary recall. Intakes in 2001 were compared with those obtained in 1980 and 1986. Nutrients selected for further examination were those implicated in the risk of CVD: saturated, monounsaturated, polyunsaturated and n-3 fatty acids, fibre and salt. An index describing the quality of adulthood diet was constructed. Multivariate logistic regression was used to identify independent childhood and adulthood determinants of the quality index. Results: The average intakes showed substantial changes since 1980. Intakes of fat and saturated fat had decreased, while the consumption of vegetables and fruit had increased. However, a great disparity was present between the recommended levels and actual intakes for many of the nutrients, particularly salt, saturated fat and fibre. Intake of fat and consumption of vegetables in childhood and physical activity in adulthood were important health behavioural determinants of the cardiovascular quality of the adult diet. Socio-demographic factors, including education of the subject and their parents, had no significant associations with diet. Conclusions: While intakes of energy and nutrients have changed favourably in Finnish young adults between 1980 and 2001 with regard to the risk of CVD, they are still far from recommended levels. Childhood diet is a significant determinant of adult diet even after 21 y. PUBLICATION ABSTRACT
To determine the tissue localization of insulin resistance in type 1 diabetic patients, whole body and regional glucose uptake rates were determined under euglycemic hyperinsulinemic conditions. Leg, ...arm, and heart glucose uptake rates were measured using positron emission tomography-derived 2-deoxy-2-18F-fluoro-D-glucose kinetics and the three-compartment model described by Sokoloff et al. (L. Sokoloff, M. Reivich, C. Kennedy, M.C. DesRosiers, C.S. Patlak, K.D. Pettigrew, O. Sakurada, and M. Shinohara. J. Neurochem. 28: 897-916, 1977) in eight type 1 diabetic patients and eight matched normal subjects. Whole body glucose uptake was quantitated by the euglycemic insulin clamp technique. Whole body glucose uptake was approximately 31% lower in the diabetic patients (P < 0.01) than in the normal subjects, thus confirming the presence of whole body insulin resistance. The rate of glucose uptake was approximately 45% lower in leg muscle when measured in the femoral region (55 +/- 7 vs. 102 +/- 13 mumol.kg muscle-1.min-1, diabetic patients vs. normal subjects, P < 0.05) and approximately 27% lower in the arm muscles (66 +/- 4 vs. 90 +/- 13 mumol.kg muscle-1.min-1, respectively, P < 0.05), whereas no difference was observed in heart glucose uptake 789 +/- 80 vs. 763 +/- 58 mumol.kg muscle-1.min-1 not significant (NS). Whole body glucose uptake correlated with glucose uptake in femoral (r = 0.93, P < 0.005) and arm muscles (r = 0.66, P < 0.05) but not with glucose uptake in the heart (r = 0.04, NS). We conclude that insulin resistance in type 1 diabetic patients is localized to skeletal muscle, whereas heart glucose uptake is unaffected.
Hyperapobetalipoproteinemia (hyperapoB) is one of the most common phenotypes in patients with premature coronary heart disease. In this study the factors that affect the expression of the hyperapoB ...phenotype were evaluated in young individuals. A cohort of 1125 children and young adults aged 9–24 years was classified into three groups by sex: (1) normal serum apolipoprotein B (apoB), (2) high apoB (≥ 90th percentile) and normal low density lipoprotein cholesterol (LDL-C < 90th), (3) high apoB and high LDL-C (≥ 90th percentile). In females, alcohol use (11, 33, 0%, in groups 1–3,
P < 0.05) and oral contraceptive use (35, 83, 47%,
P < 0.01) were significantly different between the groups and the highest frequencies were seen in the hyperapoB group (group 2). In both sexes smoking tended to be more common in the hyperapoB group (29, 43, 18%,
P = 0.14). The two hyperapoB definition criteria (high apoB and low
LDL-C
apoB
ratio) were studied with multiple linear regression analyses. Oral contraceptive use correlated positively with apoB values (coefficient
β = 0.101,
R
2 = 2.1%,
P < 0.01) and negatively with
LDL-C
apoB
ratio (
β = −0.134,
R
2 = 3.3%,
P < 0.001). Alcohol use (
β = −0.072,
R
2 = 2.9%,
P < 0.001) and smoking (
β = −0.050,
R
2 = 1.0%,
P < 0.05) correlated negatively with
LDL-C
apoB
ratio. Prevalence of the hyperapoB phenotype was 4.4%. According to the results, the expression of the hyperapoB phenotype may be influenced by common lifestyle habits. This should be considered if high risk young individuals are identified through the expression of the hyperapoB phenotype.
We evaluated a new, highly sensitive time-resolved fluoroimmunoassay for thyrotropin (TSH) in serum. This direct immunometric "sandwich"-type assay involves two monoclonal antibodies against TSH, one ...immobilized, the other labeled with europium. Extremely high specific activity of the label and the use of labeled antibody in large excess make the method sensitive enough to measure TSH values falling below the normal reference interval. The standard curve is nearly linear over a wide range of TSH concentrations (standard concentrations range from 0.25 to 324 milli-int. units/L). The lowest concentration detectable was 25 micro-int. units/L. The CV for the assay was less than 6% at 0.5 milli-int. unit/L or higher, 11.3% at 0.1 milli-int. unit/L. For a CV of 10% the lower limit of the working range would be around 0.1 milli-int. unit/L. The interassay CV was 6.7 to 11.8% for TSH concentrations of 0.31 to 19.6 milli-int. units/L. The 95% confidence interval for sera from 111 healthy persons was 0.6-3.8 (range 0.3-3.8) milli-int. units/L. For hyperthyroid patients and thyroid cancer patients treated with thyroxin after thyroidectomy, serum TSH values were all below the reference interval (most were less than 25 micro-int. units/L).
Individuals with exceptional longevity and their offspring have significantly larger high-density lipoprotein concentrations (HDL-C) particle sizes due to the increased homozygosity for the I405V ...variant in the cholesteryl ester transfer protein (
gene. In this study, we investigate the association of
and HDL-C further to identify novel, independent
variants associated with HDL-C in humans.
We performed a meta-analysis of HDL-C within the
region using 59,432 individuals imputed with 1000 Genomes data. We performed replication in an independent sample of 47,866 individuals and validation was done by Sanger sequencing.
The meta-analysis of HDL-C within the
region identified five independent variants, including an exonic variant and a common intronic insertion. We replicated these 5 variants significantly in an independent sample of 47,866 individuals. Sanger sequencing of the insertion within a single family confirmed segregation of this variant. The strongest reported association between HDL-C and
variants, was rs3764261; however, after conditioning on the five novel variants we identified the support for rs3764261 was highly reduced (
=3.179 mg/dl (
value=5.25×10
),
=0.859 mg/dl (
value=9.51×10
)), and this finding suggests that these five novel variants may partly explain the association of
with HDL-C. Indeed, three of the five novel variants (rs34065661, rs5817082, rs7499892) are independent of rs3764261.
The causal variants in
that account for the association with HDL-C remain unknown. We used studies imputed to the 1000 Genomes reference panel for fine mapping of the
region. We identified and validated five variants within this region that may partly account for the association of the known variant (rs3764261), as well as other sources of genetic contribution to HDL-C.
PDF
