Identification of an apolipoprotein(e) variant associated with type III hyperlipoproteinaemia in an indigenous Australian

As a result of testing for lipid and apolipoprotein(e) (apo E) phenotype st atus of an indigenous Australian community, an apo E variant associated wit h type III hyperlipoproteinaemia has been identified. Apo E phenotype was d etermined by analysis of VLDL by isoelectric focusing, and genotype on DNA amplified by polymerase chain reaction, using two different restriction enz yme isotyping assays. Phenotypes and genotypes were discordant in samples f rom two subjects and an abnormal-sized restriction fragment was also observ ed in their genotyping gel patterns. DNA sequencing studies revealed this w as due to a single nucleotide deletion. 3817delC, at amino acid 136 on apo E. This resulted in a new reading frame and the premature termination of th e apo E protein due to a stop codon (TGA) at nucleotide 4105. The variant a po E null allele showed a recessive mode of inheritance and, in combination with the E2 allele, resulted in the type III hyperlipoproteinaemic phenoty pe but when inherited with the E4 allele had no marked effect on plasma lip ids.