Association of adipose and red blood cell lipids with severity of dominant Stargardt macular dystrophy (STGD3) secondary to an ELOVL4 mutation.
OBJECTIVE
To determine whether adipose and red blood cell membrane lipids, particularly long-chain polyunsaturated fatty acids such as docosahexaenoic acid and eicosapentaenoic acid, are significantly correlated with phenotype in a family with autosomal dominant Stargardt macular dystrophy (gene locus STGD3). A mutation in the ELOVL4 gene is responsible for the macular dystrophy in this family, and its disease-causing mechanism may be its possible involvement in fatty acid elongation in the retina.


METHODS
The subjects in this study included 18 adult family members known to have a 2-base pair deletion in the ELOVL4 gene. Control subjects included 26 family members without the mutation. Each subject received a complete eye examination including fundus photographs, the results of which were used to grade the severity of macular dystrophy on a 3-tier scale. Red blood cell membrane and adipose tissue lipids were analyzed as an indication of short-term and long-term dietary fatty acid intake.


RESULTS
When adipose lipids were analyzed, there was a significant inverse relationship between phenotypic severity and the level of eicosapentaenoic acid (r = -0.54; P = .04). When red blood cell lipids were analyzed, there were significant inverse relationships between phenotypic severity and levels of eicosapentaenoic acid (r = -0.55; P = .02) and docosahexaenoic acid (r = -0.48; P = .04).


CONCLUSIONS
These results indicate that the phenotypic diversity in this family may be related to differences in dietary fat intake as reflected by adipose and red blood cell lipids.


CONCLUSIONS
This study demonstrates that dietary factors can influence the severity of an inherited human macular dystrophy.
Department of Foods and Nutrition, University of Utah, Salt Lake City, USA.
Amy F
AF
Hubbard
E Wayne
EW
Askew
Nanda
N
Singh
Mark
M
Leppert
Paul S
PS
Bernstein
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000368:Aged; D004034:Diet Surveys; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005799:Genes, Dominant; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012720:Severity of Illness Index
D004042:Dietary Fats, Unsaturated; C418975:ELOVL4 protein, human; D005136:Eye Proteins; D008565:Membrane Proteins; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid