Purchase this article with an account.
S Schmidt, C Allen, EA Postel, A Agarwal, RM Domurath, M Hogan, JL Haines, MA Pericak-Vance, JR Gilbert; An Analysis of Allelic Variation in the ABCA4 Gene in Multiplex ARM Patients and Controls . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1845.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose:To investigate whether variants in the gene encoding ABCR (ABCA4), a photoreceptor-specific ATP-binding cassette transporter, are associated with an increased risk of age-related maculopathy (ARM). Methods:Denaturing high-performance liquid chromatography (DHPLC) was used to screen all 50 exons of the ABCA4 gene in a total of 256 individuals. Samples were grouped into pools of size 3 to 5 for rapid processing. Individual samples from pools in which variants were detected were then bidirectionally sequenced. The screened samples included 164 multiplex ARM patients from 70 families with two or more affected relatives, diagnosed according to slightly modified criteria from the International ARM Study Group. Of the 164 patients (mean age 73.4 years), 22.0% were diagnosed with early ARM, 20.1% with atrophic, and 57.9% with neovascular ARM. In addition, we also screened 33 clinically examined unaffected family members (25 without any or with only small non-extensive drusen, grade1) and 59 clinically examined, ethnically matched unrelated controls (53 grade 1, mean age 66.8 years). Results:We did not detect the variants D2177N and G1961E previously reported to be associated with increased ARM risk in any of our 256 samples. In agreement with previous studies, the ABCA4 gene exhibited a large degree of sequence variation, with about 30 detected exonic or intronic variants. We identified several of the variants previously reported in populations of ARM patients or controls, but also observed novel changes. The final analysis and interpretation of our variation screen is still ongoing, but preliminary results do not indicate a significantly higher frequency of variants in exons 30, 42 and 48 (alone or in combination) in patients compared to controls. Conclusion:The possible association of ABCA4 variants and ARM risk has been controversial since the hypothesis was initially proposed by Allikmets et al. (1997). The preliminary analysis of our comprehensive variation screen in a clinically well-characterized study population did not confirm the association of the D2177N, G1961E or any other variants with an increased risk of ARM. A catalogue of exonic and intronic variants will be presented for our study population.
This PDF is available to Subscribers Only