A novel apolipoprotein C-III variant, apoC-III(Gln38–>Lys), associated with moderate hypertriglyceridemia in a large kindred of Mexican origin

is a major protein component of very low density lipoproteins (VLDL), chylomicrons, and a minor component of high density lipoproteins (HDL).Studies of naturally occurring human variants of apoC-111 will help in adding to our understanding of the physiological function of this apolipoprotein.Using isoelectric fo- cusing (IEF) of VLDL fractions we screened over 2500 lipid clinic patients and have identified an individual with a novel apoC-111 variant.DNA sequencing revealed the variant to be a Lys for GIn exchange at amino acid residue 38 due to an A for C substitution in exon 3.This was confirmed by NH,-terminal protein sequence analysis.The mutant Lys38 variant was present in VLDL at about the same level as the normal form although the total amount of apoC-111 was increased by 34%.The proband, a 16-year-old boy of Mexican origin, had a plasma level of total triglycerides above the 95th percentile for his age.Family studies revealed a further 16 individuals who were heterozygous for this apoC-III(Gln38 -+ Lys) variant.Compared to 21 unaffected relatives, the 17 heterozygous subjects had a statistically significant 32% elevation of their plasma levels of triglycerides when adjusted for age, sex, body mass index, and lifestyle.Other lipid and lipoprotein values were unaf€ected.lThe presence of an additional positive charge at residue 38 suggests that this residue is involved in the function of apoC-111.The elevation of plasma levels of triglycerides supports the view that apoC-111 is involved in the regulation of the catabolism of triglyceride-rich lipoproteins.-Pullinger,