ABCA7 p.Thr319Ala
| Predicted by SNAP2: | A: N (82%), C: N (78%), D: N (78%), E: N (82%), F: N (61%), G: N (66%), H: N (87%), I: N (78%), K: N (87%), L: N (72%), M: N (78%), N: N (87%), P: N (78%), Q: N (82%), R: N (78%), S: N (93%), V: N (53%), W: D (63%), Y: N (66%), |
| Predicted by PROVEAN: | A: N, 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, V: N, W: N, Y: N, |
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[hide] Homozygosity for the 168His variant of the minor h... Eur J Immunol. 2005 Jan;35(1):305-17. Harangi M, Kaminski WE, Fleck M, Orso E, Zeher M, Kiss E, Szekanecz Z, Zilahi E, Marienhagen J, Aslanidis C, Paragh G, Bolstad AI, Jonsson R, Schmitz G
Homozygosity for the 168His variant of the minor histocompatibility antigen HA-1 is associated with reduced risk of primary Sjogren's syndrome.
Eur J Immunol. 2005 Jan;35(1):305-17., [PMID:15593299]
Abstract [show]
The genes for the human ATP-binding cassette (ABC) transporter ABCA7 and the minor histocompatibility antigen HA-1 are juxtaposed in close proximity on chromosome 19p13.3. The multispan transmembrane protein ABCA7 contains an extracellular domain that is recognized by antisera from patients with Sjogren's syndrome ("Sjogren-epitope"). Recent work from our laboratory demonstrating the involvement of ABCA7 in cellular ceramide and phosphatidylserine export suggests a role for this transporter in programmed cell death. In HA-1, a protein of unknown function, a His/Arg polymorphism (His168Arg), which constitutes the immunologic target for HA-1-specific cytotoxic T cells, has been causatively linked to graft-versus-host disease after allogeneic stem cell transplantation. Because these findings suggest a potential implication of ABCA7 and HA-1 in immune processes, we tested the hypothesis that allelic variants in both genes are associated with autoimmune disorders. We identified a total of 31 exonic single-nucleotide polymorphisms (SNP) in the ABCA7/HA-1 gene complex, nine of which represent non-synonymous nucleotide alterations. Genotypes of ABCA7 and HA-1 SNP were determined in three distinct Caucasian populations of patients with primary Sjogren's syndrome and ethnically matched controls. Comparison of allele frequencies between these groups revealed that the incidence of the HA-1 168His allele is significantly lower in Sjogren's syndrome patients than in controls (p<0.003). In contrast, the frequencies of all ABCA7 allelic variants and additional HA-1 polymorphisms were similar in patients and controls. In cohorts of patients with systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis, no significant differences in the frequencies of ABCA7 and HA-1 allelic variants were observed relative to controls. Our results suggest that the HA-1 168His variant is associated with reduced susceptibility to primary Sjogren's syndrome.
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No. Sentence Comment
39 Of these, six represent non-synonymous nucleotide alterations (A955G, A1184G, G1388A, A2153C, C4580G, A5057G) giving rise to the following amino acid substitutions: Thr319Ala, His395Arg, Arg463His, Asn718Thr, Ala1527Gly, and Gln1686Arg, respectively.
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ABCA7 p.Thr319Ala 15593299:39:165
status: NEW46 Genotyping of the ABCA7 allelic variants in the German control population revealed a consistent linkage pattern for the ABCA7 SNP Thr319Ala (nt 955), His395Arg (nt 1184), Arg463His (nt 1388), Asn718Thr (nt 2153), and Gln1686Arg (nt 1686), in each individual tested (not shown, Table 2).
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ABCA7 p.Thr319Ala 15593299:46:130
status: NEW69 Comparison of the genotype frequencies of the ABCA7 SNP A955G (Thr319Ala), A1184G (His395Arg), G1388A (Arg463His), A2153C (Asn718Thr), C4580G (Ala1527Gly), and A5057G (Gln1686Arg) in the Norwegian, Hungarian and German study populations did not reveal consistent, significant differences between patients with Sjögren's syndrome and controls (Table 4).
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ABCA7 p.Thr319Ala 15593299:69:63
status: NEW102 Analysis of the population frequencies of the ABCA7 allelic variants revealed consistent linkage of five polymorphic sites, including Thr319Ala, His395Arg, Arg463His, Asn718Thr, and Gln1686Arg.
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ABCA7 p.Thr319Ala 15593299:102:134
status: NEW107 Three of the linked polymorphisms (Thr319Ala- His395Arg-Arg463His) are localized within the putative first extracellular loop of ABCA7, which contains the epitope SS-N. The latter has been reported to represent an autoantigen ("SS-N") in Sjögren's syndrome patients [10, 11].
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ABCA7 p.Thr319Ala 15593299:107:35
status: NEW