An increased incidence of apolipoprotein E2/E2 and E4/E4 in retinitis pigmentosa

Previous studies from our laboratory have shown that retinitis pigmentosa (RP), a family of hereditary retinal degenerations, is often accompanied by abnormal levels of cholesterol or polyunsaturated fatty acids. The requirement of the retina for n−3 fatty acids is well known, and a defect in the supply of these lipids ( e.g. , by apolipoproteins) could affect the course of the disease. The present study confirms and extends a report on apolipoprotein E (apo E) isoforms in German RP patients [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 families. The findings revealed a 4‐fold increase in the incidence of E2/E2 and an 8‐fold increase in E4/E4 compared to a Scottish control population. These increases were statistically significant at the P <0.05 and P <0.01 levels, respectively. To investigate the possibility that some of these apparent E2/E2 or E4/E4 phenotypes might actually be new apo E mutations, we examined the behavior of the apo E on sodium dodecyl sulfate‐polyacrylamide gels (E2 migrates anomalously) and on isoelectric focusing gels following cysteamine modification of cysteines. These studies showed that two RP patients possibly had new apo E mutations, though amino‐terminal sequence analysis revealed no changes in the sequence of the first 19 residues; further sequence analysis is obviously warranted.