WEKO3
インデックスリンク
アイテム
Non-synonymous single-nucleotide variations of the human oxytocin receptor gene and autism spectrum disorders: a case-control study in a Japanese population and functional analysis.
http://hdl.handle.net/2297/48354
http://hdl.handle.net/2297/483540344c070-5190-4f40-bb05-ff5471a4a016
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
ME-PR-YAMAGISHI-M-22.pdf (1.9 MB)
|
|
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2017-10-03 | |||||
| タイトル | ||||||
| タイトル | Non-synonymous single-nucleotide variations of the human oxytocin receptor gene and autism spectrum disorders: a case-control study in a Japanese population and functional analysis. | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| 著者 |
Ma, Wen-Jie
× Ma, Wen-Jie× Hashii, Minako× Munesue, Toshio× Hayashi, Kenshi× Yagi, Kunimasa× Yamagishi, Masakazu |
|||||
| 書誌情報 |
Molecular Autism 巻 4, 号 1, p. 22, 発行日 2013-07-01 |
|||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 2040-2392 | |||||
| DOI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1186/2040-2392-4-22 | |||||
| 出版者 | ||||||
| 出版者 | BioMed Central | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Background: The human oxytocin receptor (hOXTR) is implicated in the etiology of autism spectrum disorders (ASDs) and is a potential target for therapeutic intervention. Several studies have reported single-nucleotide polymorphisms (SNPs) of the OXTR gene associated with ASDs. These SNPs, however, reside outside the protein-coding region. Not much is known about genetic variations that cause amino acid substitutions that alter receptor functions. Methods. Variations in the OXTR gene were analyzed in 132 ASD patients at Kanazawa University Hospital in Japan and 248 unrelated healthy Japanese volunteers by re-sequencing and real-time polymerase chain reaction-based genotyping. Functional changes in variant OXTRs were assessed by radioligand binding assay and measurements of intracellular free calcium concentrations ([Ca§ssup§2+§esup§]§ssub§i§esub§) and inositol 1,4,5-trisphosphate (IP§ssub§3§esub§) levels. Results: Six subjects (4.5%) in the ASD group and two in the control group (0.8%) were identified as heterozygotes carrying the R376G variation (rs35062132; c.1126C>G); one individual from the ASD group (0.8%) and three members of the control group (1.2%) were found to be carrying R376C (c.1126C>T). The C/G genotype significantly correlated with an increased risk of ASDs (odds ratio (OR) = 5.83; 95% confidence interval (CI) = 1.16 to 29.33; P = 0.024, Fisher's exact test). Consistently, the G allele showed a correlation with an increased likelihood of ASDs (OR = 5.73; 95% CI = 1.15 to 28.61; P = 0.024, Fisher's exact test). The frequencies of the C/T genotype and the T allele in the ASD and control groups did not differ significantly. We also examined changes in agonist-induced cellular responses mediated by the variant receptors hOXTR-376G and hOXTR-376C. OXT-induced receptor internalization and recycling were faster in hOXTR-376G-expressing HEK-293 cells than in cells expressing hOXTR-376R or hOXTR-376C. In addition, the elevation in [Ca§ssup§2+§esup§]§ssub§i§esub§ and IP§ssub§3§esub§ formation decreased in the cells expressing hOXTR-376G and hOXTR-376C tagged with enhanced green fluorescent protein (EGFP), in comparison with the cells expressing the common-type hOXTR-376R tagged with EGFP. Conclusions: These results suggest that the rare genetic variation rs35062132 might contribute to the pathogenesis of ASDs, and could provide a molecular basis of individual differences in OXTR-mediated modulation of social behavior. © 2013 Ma et al.; licensee BioMed Central Ltd. | |||||
| 権利 | ||||||
| 権利情報 | © 2013 Ma et al.; licensee BioMed Central Ltd. | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
