Genetic influences contributing to LDL particle size in familial combined hyperlipidaemia.

The nature of the genetic and environmental factors influencing low density lipoprotein (LDL) particle size in patients with familial combined hyperlipidaemia (FCHL) is under debate. We measured LDL peak particle size in 553 subjects belonging to 48 Finnish FCHL families. Individuals with high triglyceride (TG) concentrations (phenotype IV) or combined hyperlipidaemia (phenotype IIB) had significantly smaller LDL particles than those with hypercholesterolaemia (phenotype IIA) or unaffected subjects (P<0.001). In stepwise regression analyses, serum TGs (r(2)=43%, P<0.001) and high density lipoprotein cholesterol (HDL-C) (r(2)=4.5%, P<0.001) were the only significant predictors of LDL peak particle size. Familial correlations support the conclusion that LDL peak particle size is familial, and most probably influenced by genes in these families. Segregation analysis of LDL peak particle size, a quantitative trait, was performed to model this genetic influence. Our results suggest a polygenic background for LDL size with a recessive major gene that may contribute to large LDL peak particle size in women. Serum TG and HDL-C concentrations predict the majority of variations in LDL particle size.

Vitamin D and attainment of peak bone mass among peripubertal Finnish girls: a 3-y prospective study.

BACKGROUND: Little is known about the effect of vitamin D status on bone gain in adolescents. OBJECTIVE: The objective was to examine whether vitamin D status is associated with accrual of bone mineral density (BMD) and bone mineral apparent density (BMAD). DESIGN: This 3-y prospective study examined the association between changes in BMD or BMAD and serum 25-hydroxyvitamin D [25(OH)D] in 171 healthy Finnish girls aged 9-15 y. Lumbar spine and femoral neck BMDs were measured by dual-energy X-ray absorptiometry. RESULTS: Baseline 25(OH)D correlated significantly with the unadjusted 3-y change in BMD at the lumbar spine (r = 0.35, P < 0.001) and femoral neck (r = 0.32, P < 0.001) in all participants. The difference from baseline in adjusted 3-y BMD accumulation between those with severe hypovitaminosis D [25(OH)D < 20 nmol/L] and those with a normal vitamin D status [25(OH)D > or = 37.5 nmol/L] was 4% (12.7%, 13.1%, and 16.7% for the lowest, middle, and highest tertiles of 25(OH)D, respectively; P for trend = 0.01) at the lumbar spine in the girls with advanced sexual maturation at baseline (n = 129). Moreover, the adjusted change in lumbar spine BMD was 27% greater in the highest vitamin D intake tertile than in the lowest tertile in the same girls (P for trend = 0.016). CONCLUSIONS: Pubertal girls with hypovitaminosis D seem to be at risk of not reaching maximum peak bone mass, particularly at the lumbar spine. Dietary enrichment or supplementation with vitamin D should be considered to ensure an adequate vitamin D status.

Recognition of familial dyslipidemias in 5-year-old children using the lipid phenotypes of parents. The STRIP project.

Adult dyslipidemias may reveal familial and, therefore, offspring dyslipidemias. We evaluated the prevalences of the adult-offspring dyslipidemias in 441 general population families composed of both parents and one 5-year-old child. Family members were classified using the 90th or 10th percentiles for hypercholesterolemia (IIA), hypertriglyceridemia (IV), combined hyperlipidemia (IIB), and low high density lipoprotein cholesterol concentration without hyperlipidemia (hypoHDL). In familial combined hyperlipidemia (FCHL), the IIB-phenotype was in one generation and one of the three hyperlipidemias in the other generation. Finally, the parental dyslipidemia phenotypes and elevated lipids (>80th percentile) that reveal offspring dyslipidemia were selected by stepwise logistic regression. Either the IIA-, IV- or hypoHDL phenotype was found in both generations in 2.8, 2.0 and 1.4% of the families, respectively. FCHL was seen in 1.8% of the families, which confirms the earlier views. The predictive values of the elevated parental cholesterol, type IV or hypoHDL parents to find type IIA, IV and hypoHDL children were low for systematic screening: 16, 13 and 15%, respectively. However, 44% of the children of IIB parents expressed hyperlipidemia (odds ratio 4.7, P=0.006). The IIB phenotype of the parent is a good predictor of the child's hyperlipidemia, and when encountered, it indicates that the lipids of the child should be studied. This would be as important as selective screening of familial hypercholesterolemia.

LDL particle size in familial combined hyperlipidemia: effects of serum lipids, lipoprotein-modifying enzymes, and lipid transfer proteins.

Small, dense LDL particles are typical for FCHL. Intravascular lipid exchange and net transfer among HDL, LDL, and triglyceride-rich lipoproteins as well as lipolysis in the VLDL-IDL-LDL cascade regulate properties of LDL. We investigated postheparin plasma activities of hepatic lipase (HL) and LPL, and plasma activities of CETP and phospholipid transfer protein (PLTP) in 191 individuals from 37 Finnish FCHL families. LDL peak particle diameter (LDL size) was measured with 2-10% gradient polyacrylamide gel electrophoresis. LDL size was significantly smaller in affected FCHL family members (n = 68) as compared with nonaffected FCHL family members (n = 78) or spouses (n = 45) (25.3 +/- 1.5 nm, 26.8 +/- 1.2 nm, and 26.6 +/- 1.2 nm, respectively, P < 0.001 for both). In affected FCHL family members, serum triglycerides were the strongest correlate for LDL size (r = -0.71, P < 0.001). In univariate correlation analysis LDL size was not associated with HL, LPL, CETP, and PLTP activities. In multivariate stepwise regression analysis, however, serum triglycerides, CETP activity, HL activity, and HDL cholesterol were significant predictors of LDL size in affected FCHL subjects (adjusted r (2) = 0.642). We conclude that serum triglyceride concentration is strongly correlated with LDL size in affected FCHL subjects. After adjustment for serum triglycerides, HL and CETP activities are associated with LDL size in FCHL.