title: An increased incidence of apolipoprotein E2/E2 and E4/E4 in retinitis pigmentosa.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Strathclyde, Glasgow, United Kingdom.
authors.forename: L
authors.initials: L
authors.lastname: Huq
authors.forename: T
authors.initials: T
authors.lastname: McLachlan
authors.forename: H M
authors.initials: HM
authors.lastname: Hammer
authors.forename: D
authors.initials: D
authors.lastname: Bedford
authors.forename: C J
authors.initials: CJ
authors.lastname: Packard
authors.forename: J
authors.initials: J
authors.lastname: Shepherd
authors.forename: C A
authors.initials: CA
authors.lastname: Converse
mesh_terms: D001057:Apolipoproteins E / Q000032:analysis*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000097:blood* / Q000453:epidemiology / Q000209:etiology; D012606:Scotland / Q000453:epidemiology; D017421:Sequence Analysis
chemical_list: D001057:Apolipoproteins E