Quantitative genetic analysis of lipoproteins in Finnish hyperlipidemic families

Abstract

P16 Familial combined hyperlipidemia (FCHL) is a common familial dyslipidemia associated with CVD risk. FCHL is characterized by higher levels of apolipoprotein B (ApoB),triglyceride (TG), smaller low-density lipoprotein particle size (LDL size) and lower high-density lipoprotein cholesterol (HDLC). The purpose of this analysis was to evaluate evidence for shared genetic effects between these fasting measurements in 365 subjects in 37 Finnish FCHL families. Mean age was 48 yrs (SD=16), 50% were male. Quantitative genetic analysis was used to evaluate the genetic (ρG) and environmental (ρE) correlations between each pair of risk factors (RF) adjusting for age and sex. Heritability was significant(p<0.02) for each RF. The ρG for each pair reflects shared genetic influences, i.e. genes that influence variation in both RF of the pair. The ρG’s for LDL size and both TG and HDLC suggest that these RF share a majority of genes in common. ρG for ApoB and TG shows that these RF also share genes in common, suggesting that at least two sets of genes influence the lipoprotein RF characterizing FCHL. Shared environmental (ρE) factors also contribute to the covariation in each pair. Using this information in mapping studies may improve power to detect genes underlying these lipoprotein abnormalities, and lead to a better understanding of genetic susceptibility to CVD in FCHL. Table 1.