Two Italian kindreds carrying the Arg136-->Ser mutation of the Apo E gene: development of premature and severe atherosclerosis in the presence of epsilon 2 as second allele

Background and Aims: Type III hyperlipoproteinemia, or dysbetalipoproteinemia, is commonly associated with apolipoprotein E2 homozygosity (Cys112, Cys158). Apo E2-Christchurch (Arg136→Ser), a rare mutation of the Apo E gene, located in the receptor-binding domain of the protein, has been found to be associated in the vast majority of cases of dysbetalipoproteinemia. Methods and Results: This is the first report of two Italian kindreds carrying the Arg136→Ser mutation. One family is a four-generation kindred from Genoa (Liguria, Italy) with a high rate of mortality due to coronary artery disease: the proband was a 51-year-old woman with previous myocardial infarction and residual angina, severe carotid atherosclerosis, peripheral arterial vascular disease and arterial hypertension. The other family was identified in Palermo (Sicily, Italy): the proband was an overweight 62-year-old man with a mixed form of hyperlipidemia. The mutation, which was identified by means of Apo E genotyping followed by direct sequencing, co-segregated with the same haplotype in the two families. Conclusions: The family histories and clinical examinations of these subjects clearly show that the Apo E Arg136→Ser variant fully expresses a type III phenotype in association with a second allele coding for Apo E2, and only partially in association with a second allele coding for Apo E4.