ABCA1 p.Ala465Val
| Predicted by SNAP2: | C: N (61%), D: N (82%), E: N (87%), F: N (57%), G: N (87%), H: N (82%), I: N (78%), K: N (87%), L: N (82%), M: N (53%), N: N (93%), P: N (82%), Q: N (93%), R: N (82%), S: N (97%), T: N (97%), V: N (82%), W: D (71%), Y: D (59%), |
| Predicted by PROVEAN: | C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: D, Y: N, |
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[hide] ABCA2 is a strong genetic risk factor for early-on... Neurobiol Dis. 2005 Feb;18(1):119-25. Mace S, Cousin E, Ricard S, Genin E, Spanakis E, Lafargue-Soubigou C, Genin B, Fournel R, Roche S, Haussy G, Massey F, Soubigou S, Brefort G, Benoit P, Brice A, Campion D, Hollis M, Pradier L, Benavides J, Deleuze JF
ABCA2 is a strong genetic risk factor for early-onset Alzheimer's disease.
Neurobiol Dis. 2005 Feb;18(1):119-25., [PMID:15649702]
Abstract [show]
Recent epidemiological, biological and genetic data indicate a relationship between cholesterol and Alzheimer's disease (AD) including the association of polymorphisms of ABCA1 (a gene that is known to participate in cholesterol and phospholipid transport) with AD prevalence. Based on these data, we postulated that genetic variation in the related and brain-specific ABCA2 gene leads to increase risk of AD. A large case-control study was conducted where the sample was randomly divided into a hypothesis-testing sample (230 cases/286 controls) and a validation sample (210 cases/233 controls). Among the 45 SNPs we tested, one synonymous SNP (rs908832) was found significantly associated with AD in both samples. Additional analyses performed on the whole sample showed a very strong association between this marker and early-onset AD (OR = 3.82, 95% C.I. = [2.00 - 7.30], P = 5 x 10(-5)). Further research is needed to understand the functional role of this polymorphism. However, together with the reported associations of AD with APOE, CYP46A1 and ABCA1, the present result adds a very significant support for the role of cholesterol and phospholipid homeostasis in AD and a rationale for testing novel cholesterol homeostasis-related therapeutic strategies in AD.
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No. Sentence Comment
82 Only one marker, SNP15 (already known as rs908832), a synonymous SNP located in exon 14, was significantly associated with Alzheimer after Bonferroni correction for 45 tests (odds ratio of 3.11 with a 95% C.I. = 1.63 - 5.91 Table 1 Annotation and allele frequencies of the 45 SNPs genotyped in ABCA2 gene SNP number NCBI dbSNP namea Position in base pairs on AL807752.10 Location Proteic variationb Common/rare alleles Allele frequency Cases (%) Controls (%) 1c rs4880189 98775 promotor - C/T 29.2 28.9 2 - 97324 intron1 - C/T 7.6 6.1 3 - 94298 intron1 - C/A 4.5 4.4 4 - 93234 intron2 - C/T 9.5 8.6 5 - 93105 intron2 - C/T 7.2 5.9 6d - 92389 exon5 R164H G/A 7.9 6.4 7e - 92343 exon5 A179A A/C 9.0 8.2 8 - 91329 intron7 - C/T 2.4 2.6 9 - 91272 intron7 - T/G 1.8 2.4 10f - 91052 intron7 - G/A 7.5 6.3 11 - 90545 intron8 - C/T 0.5 0.4 12d - 90329 exon9 A465V C/T 0.0 0.6 13 rs2176675 89729 intron9 - G/A 24.5 20.8 14 - 88103 intron13 - A/G 10.9 10.0 15e rs908832 87994 exon14 D679D C/T 8.0 3.1 16f - 87896 intron14 - G/T 1.2 1.0 17f rs6420279 87688 intron15 - T/C 39.5 38.0 18f - 87111 intron17 - C/T 2.9 4.2 19f rs6560657 86158 intron20 - G/A 2.0 2.6 20 rs10781532 84524 intron25 - A/G 3.3 2.7 21d - 83974 exon27 V1423F G/T 1.4 0.2 22 - 83790 intron27 - G/A 0.2 1.3 23 rs10781531 83775 intron27 - G/A 1.9 2.8 24 rs10870162 83649 intron27 - C/T 27.2 24.7 25 rs4880188 83352 intron28 - G/A 30.7 31.9 26 - 82991 exon29 V1614I G/A 0.9 0.2 27d - 82500 exon31 G1712S G/A 0.2 0.4 28 - 82401 intron31 - C/T 0.5 0.4 29 - 82196 intron32 - C/T 41.9 43.4 30 rs2271863 82023 intron33 - G/A 27.0 25.2 31e rs2271862 81869 exon34 H1824H T/C 27.0 27.2 32f - 81526 intron35 - C/T 0.4 0.6 33e - 81405 exon36 V1921V G/T 1.2 1.4 34 rs2292920 81329 intron36 - G/A 13.6 13.8 35e - 80651 exon39 A2035A C/T 6.1 8.0 36e - 80232 exon40 A2092A G/A 3.1 1.5 37f - 80126 intron40 - C/A 1.0 0.7 38e rs7048567 79547 exon43 L2230L C/T 29.4 27.0 39 rs4880187 78307 intron47 - C/G 3.6 4.0 40 rs4880186 78296 intron47 - G/C 2.5 3.7 41 rs10870161 77724 exon48 - C/T 2.4 4.0 42 - 77676 exon48 - C/T 26.4 23.9 43 - 77500 exon48 - C/T 0.9 1.6 44 rs4335222 77491 exon48 - G/T 1.1 1.4 45 rs7036668 77401 exon48 - C/T 1.9 3.2 a Name provided when SNP exists in NCBI dbSNP database.
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ABCA1 p.Ala465Val 15649702:82:850
status: NEW83 Only one marker, SNP15 (already known as rs908832), a synonymous SNP located in exon 14, was significantly associated with Alzheimer after Bonferroni correction for 45 tests (odds ratio of 3.11 with a 95% C.I. = 1.63 - 5.91 Table 1 Annotation and allele frequencies of the 45 SNPs genotyped in ABCA2 gene SNP number NCBI dbSNP namea Position in base pairs on AL807752.10 Location Proteic variationb Common/rare alleles Allele frequency Cases (%) Controls (%) 1c rs4880189 98775 promotor - C/T 29.2 28.9 2 - 97324 intron1 - C/T 7.6 6.1 3 - 94298 intron1 - C/A 4.5 4.4 4 - 93234 intron2 - C/T 9.5 8.6 5 - 93105 intron2 - C/T 7.2 5.9 6d - 92389 exon5 R164H G/A 7.9 6.4 7e - 92343 exon5 A179A A/C 9.0 8.2 8 - 91329 intron7 - C/T 2.4 2.6 9 - 91272 intron7 - T/G 1.8 2.4 10f - 91052 intron7 - G/A 7.5 6.3 11 - 90545 intron8 - C/T 0.5 0.4 12d - 90329 exon9 A465V C/T 0.0 0.6 13 rs2176675 89729 intron9 - G/A 24.5 20.8 14 - 88103 intron13 - A/G 10.9 10.0 15e rs908832 87994 exon14 D679D C/T 8.0 3.1 16f - 87896 intron14 - G/T 1.2 1.0 17f rs6420279 87688 intron15 - T/C 39.5 38.0 18f - 87111 intron17 - C/T 2.9 4.2 19f rs6560657 86158 intron20 - G/A 2.0 2.6 20 rs10781532 84524 intron25 - A/G 3.3 2.7 21d - 83974 exon27 V1423F G/T 1.4 0.2 22 - 83790 intron27 - G/A 0.2 1.3 23 rs10781531 83775 intron27 - G/A 1.9 2.8 24 rs10870162 83649 intron27 - C/T 27.2 24.7 25 rs4880188 83352 intron28 - G/A 30.7 31.9 26 - 82991 exon29 V1614I G/A 0.9 0.2 27d - 82500 exon31 G1712S G/A 0.2 0.4 28 - 82401 intron31 - C/T 0.5 0.4 29 - 82196 intron32 - C/T 41.9 43.4 30 rs2271863 82023 intron33 - G/A 27.0 25.2 31e rs2271862 81869 exon34 H1824H T/C 27.0 27.2 32f - 81526 intron35 - C/T 0.4 0.6 33e - 81405 exon36 V1921V G/T 1.2 1.4 34 rs2292920 81329 intron36 - G/A 13.6 13.8 35e - 80651 exon39 A2035A C/T 6.1 8.0 36e - 80232 exon40 A2092A G/A 3.1 1.5 37f - 80126 intron40 - C/A 1.0 0.7 38e rs7048567 79547 exon43 L2230L C/T 29.4 27.0 39 rs4880187 78307 intron47 - C/G 3.6 4.0 40 rs4880186 78296 intron47 - G/C 2.5 3.7 41 rs10870161 77724 exon48 - C/T 2.4 4.0 42 - 77676 exon48 - C/T 26.4 23.9 43 - 77500 exon48 - C/T 0.9 1.6 44 rs4335222 77491 exon48 - G/T 1.1 1.4 45 rs7036668 77401 exon48 - C/T 1.9 3.2 a Name provided when SNP exists in NCBI dbSNP database.
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ABCA1 p.Ala465Val 15649702:83:850
status: NEW