AN INCREASED INCIDENCE OF APOLIPOPROTEIN E2 E2 AND E4/E4 IN RETINITIS-PIGMENTOSA/

Previous studies from our laboratory have shown that retinitis pigment osa (RP), a family of hereditary retinal degenerations, is often accom panied by abnormal levels of cholesterol or polyunsaturated fatty acid s. The require ment of the retina for n-3 fatty acids is well known, a nd a defect in the supply of these lipids (e.g., by apolipoproteins) c ould affect the course of the disease. The present study confirms and extends a report on apolipoprotein E (apo E) isoforms in German RP pat ients [Jahn, Oette, Esser, Bergmann, and Leiss, (1987) Ophthalmic Res. 19, 285-288] which showed a tenfold increased frequency of the E2/E2 phenotype compared to the average German population. In our study, apo E phenotypes were determined in the probands of 100 Scottish RP famil ies. The findings revealed a 4-fold increase in the incidence of E2/E2 and an and fold increase in E4/E4 compared to a Scottish control popu lation. These increases were statistically significant at the P < 0.05 and P < 0.01 levels, respectively. To investigate the possibility tha t some of these apparent E2/E2 or E4/E4 phenotypes might actually be n ew apo E mutations, we examined the behavior of the apo E on sodium do decyl sulfate-polyacrylamide gels (E2 migrates anomalously) and on iso electric focusing gels following cysteamine modification of cysteines. These studies showed that two RP patients possibly had new apo E muta tions, though amino-terminal sequence analysis revealed no changes in the sequence of the first 19 residues; further sequence analysis is ob viously warranted.