Abstract
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 (r2=43%, P<0.001) and high density lipoprotein cholesterol (HDL-C) (r2=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.
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Acknowledgements
We thank Seppo Sarna for statistical advice, and Helinä Perttunen-Nio, Ritva Marjanen, and Leena Lehikoinen for technical assistance. The results of familial correlations and segregation analyses were obtained by means of the program package SAGE which is supported by US Public Health Services Resource grant (1 P41 RR03655) from the National Center for Research Resources. This work was supported by grants from the Finnish Academy, Finnish Heart Foundation, Duodecim Foundation, Maud Kuistila Foundation, Helsinki University Central Hospital Research Foundation, and European Commission contract ‘European Multicenter Study on Familial Dyslipidemias With Premature Coronary Heart Disease (EUFAM)’, contract number BMH4-CT96-1678. P Pajukanta, RM Cantor and L Peltonen were supported in part by the National Institutes of Health Program Project grant HL-28481.
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Vakkilainen, J., Pajukanta, P., Cantor, R. et al. Genetic influences contributing to LDL particle size in familial combined hyperlipidaemia. Eur J Hum Genet 10, 547–552 (2002). https://doi.org/10.1038/sj.ejhg.5200844
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DOI: https://doi.org/10.1038/sj.ejhg.5200844
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