RARE APOLIPOPROTEIN-E VARIANT IDENTIFIED IN A PATIENT WITH TYPE-III HYPERLIPEMIA

We report a rare apolipoprotein E variant in an Irish female with Type III hyperlipidaemia who has the phenotype E2E1 as determined by isoel ectric focusing. Sequence analysis of the apolipoprotein E gene from t he proband and from four other family members, using DNA amplified by the polymerase chain reaction, demonstrated the presence of a point mu tation in the common epsilon2 allele with a G-->A transition at nucleo tide 3791. This was confirmed by digestion with the restriction endonu clease TaqI, which cuts at a new site within the apolipoprotein E gene , created by the base change. This mutation results in a substitution of aspartic acid for glycine at position 127 of the mature protein. We believe this to be the first description of this apolipoprotein E var iant in a family from the British Isles. The mutation appears to be 'r ecessive' with respect to the expression of Type III hyperlipidaemia, although it may be somewhat more potent in this regard than the parent epsilon2 allele. The Type III hyperlipidaemia is responsive to treatm ent with diet and gemfibrozil.