Association Of Adipose And Red Blood Cell Lipids With Severity Of Dominant Stargardt Macular Dystrophy

Abstract

Abstract: : Purpose: To determine whether adipose and red blood cell lipids, particularly long–chain polyunsaturated fatty acids, such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are significantly correlated with phenotype in a family with autosomal dominant Stargardt–like macular dystrophy. A mutation in the ELOVL4 gene is responsible for the macular dystrophy present in this family via its possible involvement in fatty acid elongation in the retina (IOVS 2001;42:3331–3336). Methods: The subjects in this study are eighteen adult family members known to have a two base–pair deletion in the ELOVL4 gene. Each subject received a complete eye examination, including fundus photographs, the results of which were used to grade the subject's severity on a three–tier scale. A blood sample was collected from each subject to examine red blood cell lipids, an indication of short–term dietary fatty acid intake. An adipose tissue sample was collected from fourteen of the eighteen subjects as an indication of long–term dietary fatty acid intake. The adipose and red blood cell lipids were analyzed using capillary gas chromatography with mass spectrometry detection (GC/MS). The subjects also completed a self–administered food frequency questionnaire. Results: When adipose lipids were analyzed, there was a significant inverse relationship between phenotypic severity and EPA (P = 0.04). When red blood cell lipids were analyzed, there were significant inverse relationships between phenotypic severity and EPA (P = 0.02) and DHA (P = 0.04). There were no significant correlations between dietary fat intake and phenotype when the food frequency questionnaire was analyzed. Conclusions: These initial results indicate that the phenotypic diversity present in this family may be related to differences in dietary fat intake, as reflected by adipose and red blood cell lipids. To our knowledge, this is the first demonstration that dietary factors can influence the severity of an inherited human macular dystrophy.

Keywords: gene modifiers • clinical (human) or epidemiologic studies: risk factor assessment • nutritional factors