Evidence that ITGB3 promoter variants increase serotonin blood levels by regulating platelet serotonin transporter trafficking (Hum Mol Genet. 2019, 28(7):1153-1161)

報告日期: 2019/11/12
報告時間: 15:10/16:00
報告學生: 傅曉婷
講評老師: 陳芃潔
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Evidence that ITGB3 promoter variants increase serotonin blood levels by regulating platelet serotonin transporter trafficking.

Stefano Gabriele et al.

Human Molecular Genetics, 2019, Vol. 28, No. 7 

Presenter: Hsiao-Ting Fu傅曉婷                         Time: 15:00~16:00 Nov. 12 2019

Commentator: Peng-Chieh Jessica Chen 陳芃潔老師                 Location: Room 602

Abstract

Autism spectrum disorder (ASD) is a clinically heterogeneous neurodevelopmental disorder that is caused by gene-environment interactions. ASD is characterized by difficulty in social interaction, communication, and repetitive behavior patterns. Genetically, autism can broadly be segregated into syndromic and non-syndromic forms. Syndromic ASD includes incidences of the disease with known genetic cause, while non-syndromic ASD with unknown genetic etiology. Elevated serotonin (5-HT) blood levels, the first biomarker identified in autism research, has been consistently found in 20–30% of patients with ASD. Hyperserotonemia is mainly due to greater 5-HT uptake into platelets, mediated by the 5-HT transporter (SERT) located at the platelet plasma membrane.ITGB3, the gene coding for part of the important platelet activation receptor αIIbβ3, has been previously identified to be related to increased SERT activity and elevated blood 5-HT levels in ASD at single nucleotide polymorphism (SNP) rs2317385. In this study, the author found out the 6 SNPs located in the gene promoter region, all in linkage disequilibrium with rs2317385. To identify the effects of these different haplotypes of ITGB3 promoter in two hematopoietic and one murine neuronal cell lines and the effects of difference genotypes of ITGB3 promoter on blood 5-HT levels and ITGB3 and SERT protein levels. The results showed the C allele at rs55827077 in enhancing ITGB3 gene promoter activity during megakaryocytic differentiation, however, murine neuronal N2A cells did not display any effect of any haplotypes on ITGB3 gene promoter activity. 176 ASD individuals with the C allele at rs55827077 and the T allele at rs3809862 were significantly higher 5-HT blood levels. No significant association was found between the two promoter SNPs rs55827077 / rs3809862 and ASDIndividuals.

Reference:

  1. Stefano Gabriele, Marco Canali, Carla Lintas, Roberto Sacco, Maria Cristina Tirindelli, Arianna Ricciardello, Antonio M Persico, Evidence that ITGB3 promoter variants increase serotonin blood levels by regulating platelet serotonin transporter trafficking, Human Molecular Genetics, Volume 28, Issue 7, 1 April 2019, Pages 1153–1161
  2. Padmakumar M, Van Raes E, Van Geet C, Freson K. Blood platelet research in autism spectrum disorders: In search of biomarkers. Res Pract Thromb Haemost. 2019;3(4):566–577.