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

• Published in: Nutrition, metabolism, and cardiovascular diseases metabolism, and cardiovascular diseases, 2003-04, Vol.13 (2), p.93-99
• Main Authors: Rolleri, M., Vivona, N., Emmanuele, G., Cefalù, A.B., Pisciotta, L., Guido, V., Noto, D., Fiore, B., Barbagallo, C.M., Notarbartolo, A., Travali, S., Bertolini, S., Averna, M.R.
• Format: Article
• Language: English
• Subjects: Alleles; apo E gene mutation; ApoE-Christchurch; Apolipoprotein E2; Apolipoproteins E - genetics; Arteriosclerosis - etiology; Arteriosclerosis - genetics; Base Sequence; cardiovascular disease; Female; Genotype; Haplotypes; Humans; Hyperlipoproteinemia Type III - complications; Hyperlipoproteinemia Type III - genetics; Lipids - blood; Male; Middle Aged; Mutation; Pedigree; Polymerase Chain Reaction; Sequence Homology; Type III hyperlipoproteinemia
• ISSN: 0939-4753; 1590-3729
• DOI: 10.1016/S0939-4753(03)80024-8

Type III hyperlipoproteinemia, or dysbetalipoproteinemia, is commonly associated with apolipoprotein E2 homozygosity (Cy Background and Aims:12, Cy Background and Aims:58). 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. 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. 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.