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An increased incidence of apolipoprotein E2/E2 and E4/E4 in retinitis pigmentosa
Author(s) -
Huq Lubna,
McLachlan Tracey,
Hammer Harold M.,
Bedford Dorothy,
Packard Christopher J.,
Shepherd James,
Converse Carolyn A.
Publication year - 1993
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02537120
Subject(s) - retinitis pigmentosa , apolipoprotein e , population , proband , isoelectric focusing , endocrinology , genetics , medicine , allele , phenotype , biology , biochemistry , chemistry , microbiology and biotechnology , gene , mutation , disease , environmental health , enzyme
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.