ABCMdb

PMID: 10880298

Allikmets R
Further evidence for an association of ABCR alleles with age-related macular degeneration. The International ABCR Screening Consortium.
Am J Hum Genet. 2000 Aug;67(2):487-91. Epub 2000 Jul 3., [PubMed]

Sentences

No. Mutations Sentence Comment

6 ABCA4 p.Gly1961Glu ABCA4 p.Asp2177Asn These two sequence changes, G1961E and D2177N, were found in one allele of ABCR in 40 patients (~3.4%), and in 13 control subjects (~0.95%). Login to comment 8 ABCA4 p.Asp2177Asn The risk of AMD is elevated approximately threefold in D2177N carriers and approximatelyP ! Login to comment 9 ABCA4 p.Gly1961Glu .0001 fivefold in G1961E carriers. Login to comment 21 ABCA4 p.Gly1961Glu ABCA4 p.Asp2177Asn We present new data on 1,218 patients with AMD and 1,258 matched controls studied at 15 centers (7 in the United States and 8 in Europe) to test the associations with AMD of two of the more common AMD-associated ABCR variants, G1961E and D2177N. Login to comment 27 ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Asp2177Asn ABCA4 p.Asp2177Asn Table 1 Association of G1961E and D2177N Alleles with AMD CENTER POPULATION AMD SAMPLES CONTROLS G1961E D2177N Dry Wet Total GP AM Total AMD (D/W) Control (GP/AM) AMD (D/W) Control (GP/AM) Boston/Salt Lake City/Baltimore Eur. Am. Login to comment 37 ABCA4 p.Gly1961Glu ABCA4 p.Asp2177Asn Genotyping of the G1961E and D2177N variants was performed by a method of choice at each center. Login to comment 42 ABCA4 p.Gly1961Glu G1961E was found in 19/1,218 (1.56%) patients with AMD compared with 4/1,258 (0.32%) control subjects (table 1) (Fisher`s two-sided exact test [Mehta and Patel 1995]; ). Login to comment 45 ABCA4 p.Gly1961Glu No statistically significant evidence of heterogeneity of odds ratios exists among analysis units, and the prevalence is higher in the AMD group in six of the eight units with at least one G1961E allele. Login to comment 46 ABCA4 p.Asp2177Asn D2177N was present in 21/1,189 (1.77%) AMD cases, compared with 8/1,258 (0.64%) controls (P = ). Login to comment 48 ABCA4 p.Asp2177Asn ABCA4 p.Asp2177Asn There was no statistically significant evidence of heterogeneity of odds ratios among units, and the prevalence of D2177N was higher in AMD cases in 8 of the 10 units with at least one D2177N allele. Login to comment 49 ABCA4 p.Gly1961Glu ABCA4 p.Asp2177Asn The combination of either G1961E or D2177N was found in 40/1,189 (3.36%) patients with AMD, compared with 12/1,258 (0.95%) control subjects (P ! Login to comment 65 ABCA4 p.Gly1961Glu ABCA4 p.Asp2177Asn Together, the G1961E and D2177N variants were present in 23/533 patients with nonexudative disease and in 17/685 with exudative lesions. Login to comment 75 ABCA4 p.Gly1961Glu ABCA4 p.Asp2177Asn For population stratification to explain the above associations at any one study center, ethnic (sub)groups in that center should both associate strongly with AMD prevalence and segregate concordantly with the prevalences of both G1961E and D2177N. Login to comment 79 ABCA4 p.Gly1961Glu ABCA4 p.Asp2177Asn It also seems unlikely that similar ethnic correlations should occur with G1961E and D2177N, which we have yet to find together in the same subject. Login to comment 80 ABCA4 p.Gly1961Glu ABCA4 p.Asp2177Asn It also seems unlikely that similar ethnic correlations should occur with G1961E and D2177N, which we have yet to find together in the same subject. Login to comment 84 ABCA4 p.Gly1961Glu The mutant G1961E protein, produced after the transfection of human embryonic kidney (293) cells with cloned cDNA, exhibits several-fold lower binding of 8-azido-ATP and inhibition of ATPase activity by retinal, as compared with the wild-type ABCR protein. Login to comment 85 ABCA4 p.Gly1961Glu ABCA4 p.Asp2177Asn The mutant G1961E protein, produced after the transfection of human embryonic kidney (293) cells with cloned cDNA, exhibits several-fold lower binding of 8- azido-ATP and inhibition of ATPase activity by retinal, as compared with the wild-type ABCR protein. Login to comment 86 ABCA4 p.Asp2177Asn The D2177N variant had no effect on 8-azido-ATP binding but exhibited a reproducible elevation in ATPase activity relative to the wild type (H. Sun, P. M. Smallwood, and J. Nathans, personal communication). Login to comment 91 ABCA4 p.Gly1961Glu ABCA4 p.Asp2177Asn In summary, new data from 15 centers in the United States and Europe independently confirm the association of ABCR alleles G1961E and D2177N with AMD. Login to comment 92 ABCA4 p.Gly1961Glu ABCA4 p.Asp2177Asn In summary, new data from 15 centers in the United States and Europe independently confirm the association of ABCR alleles G1961E and D2177N with AMD. Login to comment