Abstract
Objective: Autism is defined as a complex neurodevelopmental disorder. Genetics plays a major role in the etiology of autism spectrum disorders (ASD). The role of the serotonin in the development of autism has been widely investigated. SLC6A4 gene (SERT or 5-HT) has an important role reuptaking of serotonin. Because of this, our study examined the expression level of SLC6A4 gene in autism patients. Methods: Thirty-four patients (26 male, 8 female) who diagnosed as autism firstly according to DSM-V criteria in the Department of child psychiatry, Erciyes University Medical Faculty and healthy 23 controls (16 male, 7 female) were enrolled in this study. Total RNA was isolated from peripheral blood samples using TRIzol. Quantitative Real-time PCR (qRT-PCR) was performed to detect SLC6A4 gene expression. Results: SLC6A4 gene expression was found statistically significant and low in autism group compared with controls (p=0,027). Conclusion: The low gene expression in the patient group implied that there is an abnormality of serotonin reuptake. According to our results, we suggest that much more studies may be planned with the expression and methylation profile of this gene combined with gene polymorphisms especially affecting the expression in larger sample sizes. J Clin Exp Invest 2015; 6 (2): 165-169
Keywords
References
- Voineagu I. Gene expression studies in autism: Moving from the genome to the transcriptome and beyond. Neurobiol Dis 2012;45:69-75.
- Eapen V. Genetic basis of autism: is there a way forward? Curr Opin Psychiatry 2011;24:226-236.
- Gabriele S, Sacco R, Persico AM. Blood serotonin levels in autism spectrum disorder: a systematic review and meta-analysis. Eur Neuropsychopharmacol 2014;24:919-929.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Washington, 5th edition, 2013.
- Sener EF, Oztop D, Ozkul Y. MTHFR Gene C677T Polymorphism in autism spectrum disorders. Genet Res Int 2014;2014:698574.
- Butler MG, Rafi SK, Hossain W, et al. Whole Exome Sequencing in Females with Autism Implicates Novel and Candidate Genes. Int J Mol Sci 2015;16:1312-1335.
- Sener EF. Association of Copy Number Variations In Autism Spectrum Disorders: A Systematic Review. Chinese Journal of Biology 2014, doi.org/10.1155/2014/713109.
- Poultney CS, Goldberg AP, Drapeau E, et al. Identification of small exonic CNV from whole-exome sequence data and application to autism spectrum disorder. Am J Hum Genet 2013;93:607-619.
- Neale BM, Kou Y, Liu L, et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature 2012;485:242-245.
- Iossifov I, Ronemus M, Levy D, et al. De novo gene disruptions in children on the autistic spectrum. Neuron 2012;74:285-299.
- Goldani AA, Downs SR, Widjaja F, et al. Biomarkers in
- autism. Front Psychiatry 2014;5:100.
- Şener EF, Özkul Y. Otizmin Genetik Temelleri. Erciyes
- Üniversitesi Sağlık Bilimleri Dergisi 2013;22:86-92.
- Guhathakurta S, Ghosh S, Sinha S, et al. Serotonin transporter promoter variants: Analysis in Indian autistic and control population. Brain Res 2006;1092:28-35.
- Jaiswal P, Guhathakurta S, Singh AS, et al. SLC6A4 markers modulate platelet 5-HT level and specific behaviors of autism: a study from an Indian population. Prog Neuropsychopharmacol Biol Psychiatry 2015; 56:196-206.
- Whyte A, Jessen T, Varney S, Carneiro AM. Serotonin
- transporter and integrin beta 3 genes interact to modulate serotonin uptake in mouse brain. Neurochem Int 2014;73:122-126.
- Huang CH, Santangelo SL. Autism and Serotonin Transporter Gene Polymorphisms: A Systematic Review and Meta-Analysis. Am J Med Genet B Neuropsychiatr Genet 2008;147B:903-913.
- Longo D, Schüler-Faccini L, Brandalize AP, et al. Influence of the 5-HTTLPR polymorphism and environmental risk factors in a Brazilian sample of patients with autism spectrum disorders. Brain Res 2009;1267:9-17.
- Koishi S, Yamamoto K, Matsumoto H, et al. Serotonin transporter gene promoter polymorphism and autism: a family-based genetic association study in Japanese population. Brain Dev 2006;28:257-260.
- Devlin B, Cook EH Jr, Coon H, et al. Autism and the serotonin transporter: the long and short of it. Mol Psychiatry 2005;10:1110-1116.
- Peralta-Leal V, Leal-Ugarte E, Meza-Espinoza JP, et al. Association of a serotonin transporter gene (SLC6A4) 5-HTTLPR polymorphism with body mass index categories but not type 2 diabetes mellitus in Mexicans. Genet Mol Biol 2012;35:589-93.
- Tordjman S, Gutknecht L, Carlier M, et al. Role of the
- serotonin transporter gene in the behavioral expression of autism. Mol Psychiatry 2001;6:434-439.
- Conroy J, Meally E, Kearney G, Fitzgerald M, Gill M, Gallagher L. Serotonin transporter gene and autism: a haplotype analysis in an Irish autistic population. Mol Psychiatry 2004;9:587-593.
- Cook EH, Courchesne R, Lord C, et al. Evidence of linkage between the serotonin transporter and autistic disorder. Mol Psychiatry 1997;2:247-250.
- Chung BH, Tao VQ, Tso WW. Copy number variation and autism: new insights and clinical implications. J Formos Med Assoc 2014;113:400-408.
- Ruggeri B, Sarkans U, Schumann G, Persico AM. Biomarkers in autism spectrum disorder: the old and the new. Psychopharmacology (Berl) 2014;231:1201-1216.
- Coutinho AM, Oliveira G, Morgadinho T, et al. Variants of the serotonin transporter gene (SLC6A4) significantly contribute to hyperserotonemia in autism. Mol Psychiatry 2004;9:264-271.
- Connors SL, Matteson KJ, Sega GAet al. Plasma serotonin in autism. Pediatr Neurol 2006; 35:182-186.
- Anderson GM, Hertzig ME, McBride PA. Brief report: Platelet-poor plasma serotonin in autism. J Autism Dev Disord 2012;42:1510-1514.
- Longo D, Schüler-Faccini L, Brandalize AP, et al. Influence of the 5-HTTLPR polymorphism and environmental risk factors in a Brazilian sample of patients with autism spectrum disorders. Brain Res 2009;1267:9-17.
- Bradley SL, Dodelzon K, Sandhu HK, Philibert RA. Relationship of serotonin transporter gene polymorphisms and haplotypes to mRNA transcription. Am J Med Genet B Neuropsychiatr Genet 2005;136B:58-61.
- Wu S, Guo Y, Jia M, et al. Lack of evidence for association between the serotonin transporter gene (SLC6A4) polymorphisms and autism in the Chinese trios. Neurosci Lett 2005;381:1-5.
- Ramoz N, Reichert JG, Corwin TE, et al. Lack of evidence for association of the serotonin transporter gene SLC6A4 with autism. Biol Psychiatry 2006;60:186-191
Abstract
Amaç: Otizm kompleks bir nörogelişimsel bozukluk olarak tanımlanmaktadır. Hastalık etiyolojisinde genetik bir taban olduğu bilinmektedir. Serotonin ve otizm arasında bir ilişki olduğu daha önce yapılan çeşitli araştırmalarla gösterilmiştir. SLC6A4 geni (SERT veya 5-HTT) serotoninin geri alımında önemli bir role sahiptir. Bu özelliğinden dolayı bu çalışmada otizm hastalarında SLC6A4 geninin ekspresyon düzeyi araştırılmıştır.
Yöntemler: Erciyes Üniversitesi Tıp Fakültesi Çocuk ve Ergen Ruh Sağlığı ve Hastalıkları Anabilim Dalı’na ilk kez başvurup, yapılan değerlendirme sonrası DSM-V kriterlerine göre otistik spektrum bozukluğu (OSB) tanısı alan 34 hasta (26 erkek, 8 kız) ve sağlıklı 23 kontrol (16 erkek, 7 kız) çalışmaya dahil edilmiştir. Gruplardan alınan periferal kan örneklerinden TRIzol yardımıyla RNA izolasyonu yapılmıştır. SLC6A4 geni ekspresyonu Kantitatif Real-Time PCR (qRT-PCR) ile belirlenmiştir.
Bulgular: SLC6A4 geni ekspresyonunun hasta grubunda kontrol grubuna göre istatistiksel olarak önemli ölçüde daha düşük olduğu bulundu (p=0,027).
Sonuç: Hasta grubunda ekspresyonun düşük olması serotoninin geri alınımında bir bozukluk olduğunu düşündürmektedir. Elde edilen bu sonuçlarımıza göre genin ekspresyonunun aynı hasta grubunda genişletilerek çalışılması, özellikle genin metilasyon durumu ve genin ekspresyonunu etkileyen polimorfizmlerin de birlikte araştırılması gerektiği düşünülmektedir.
Anahtar kelimeler: Otizm, ekspresyon, SLC6A4, gen, serotonin
Keywords
References
- Voineagu I. Gene expression studies in autism: Moving from the genome to the transcriptome and beyond. Neurobiol Dis 2012;45:69-75.
- Eapen V. Genetic basis of autism: is there a way forward? Curr Opin Psychiatry 2011;24:226-236.
- Gabriele S, Sacco R, Persico AM. Blood serotonin levels in autism spectrum disorder: a systematic review and meta-analysis. Eur Neuropsychopharmacol 2014;24:919-929.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Washington, 5th edition, 2013.
- Sener EF, Oztop D, Ozkul Y. MTHFR Gene C677T Polymorphism in autism spectrum disorders. Genet Res Int 2014;2014:698574.
- Butler MG, Rafi SK, Hossain W, et al. Whole Exome Sequencing in Females with Autism Implicates Novel and Candidate Genes. Int J Mol Sci 2015;16:1312-1335.
- Sener EF. Association of Copy Number Variations In Autism Spectrum Disorders: A Systematic Review. Chinese Journal of Biology 2014, doi.org/10.1155/2014/713109.
- Poultney CS, Goldberg AP, Drapeau E, et al. Identification of small exonic CNV from whole-exome sequence data and application to autism spectrum disorder. Am J Hum Genet 2013;93:607-619.
- Neale BM, Kou Y, Liu L, et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature 2012;485:242-245.
- Iossifov I, Ronemus M, Levy D, et al. De novo gene disruptions in children on the autistic spectrum. Neuron 2012;74:285-299.
- Goldani AA, Downs SR, Widjaja F, et al. Biomarkers in
- autism. Front Psychiatry 2014;5:100.
- Şener EF, Özkul Y. Otizmin Genetik Temelleri. Erciyes
- Üniversitesi Sağlık Bilimleri Dergisi 2013;22:86-92.
- Guhathakurta S, Ghosh S, Sinha S, et al. Serotonin transporter promoter variants: Analysis in Indian autistic and control population. Brain Res 2006;1092:28-35.
- Jaiswal P, Guhathakurta S, Singh AS, et al. SLC6A4 markers modulate platelet 5-HT level and specific behaviors of autism: a study from an Indian population. Prog Neuropsychopharmacol Biol Psychiatry 2015; 56:196-206.
- Whyte A, Jessen T, Varney S, Carneiro AM. Serotonin
- transporter and integrin beta 3 genes interact to modulate serotonin uptake in mouse brain. Neurochem Int 2014;73:122-126.
- Huang CH, Santangelo SL. Autism and Serotonin Transporter Gene Polymorphisms: A Systematic Review and Meta-Analysis. Am J Med Genet B Neuropsychiatr Genet 2008;147B:903-913.
- Longo D, Schüler-Faccini L, Brandalize AP, et al. Influence of the 5-HTTLPR polymorphism and environmental risk factors in a Brazilian sample of patients with autism spectrum disorders. Brain Res 2009;1267:9-17.
- Koishi S, Yamamoto K, Matsumoto H, et al. Serotonin transporter gene promoter polymorphism and autism: a family-based genetic association study in Japanese population. Brain Dev 2006;28:257-260.
- Devlin B, Cook EH Jr, Coon H, et al. Autism and the serotonin transporter: the long and short of it. Mol Psychiatry 2005;10:1110-1116.
- Peralta-Leal V, Leal-Ugarte E, Meza-Espinoza JP, et al. Association of a serotonin transporter gene (SLC6A4) 5-HTTLPR polymorphism with body mass index categories but not type 2 diabetes mellitus in Mexicans. Genet Mol Biol 2012;35:589-93.
- Tordjman S, Gutknecht L, Carlier M, et al. Role of the
- serotonin transporter gene in the behavioral expression of autism. Mol Psychiatry 2001;6:434-439.
- Conroy J, Meally E, Kearney G, Fitzgerald M, Gill M, Gallagher L. Serotonin transporter gene and autism: a haplotype analysis in an Irish autistic population. Mol Psychiatry 2004;9:587-593.
- Cook EH, Courchesne R, Lord C, et al. Evidence of linkage between the serotonin transporter and autistic disorder. Mol Psychiatry 1997;2:247-250.
- Chung BH, Tao VQ, Tso WW. Copy number variation and autism: new insights and clinical implications. J Formos Med Assoc 2014;113:400-408.
- Ruggeri B, Sarkans U, Schumann G, Persico AM. Biomarkers in autism spectrum disorder: the old and the new. Psychopharmacology (Berl) 2014;231:1201-1216.
- Coutinho AM, Oliveira G, Morgadinho T, et al. Variants of the serotonin transporter gene (SLC6A4) significantly contribute to hyperserotonemia in autism. Mol Psychiatry 2004;9:264-271.
- Connors SL, Matteson KJ, Sega GAet al. Plasma serotonin in autism. Pediatr Neurol 2006; 35:182-186.
- Anderson GM, Hertzig ME, McBride PA. Brief report: Platelet-poor plasma serotonin in autism. J Autism Dev Disord 2012;42:1510-1514.
- Longo D, Schüler-Faccini L, Brandalize AP, et al. Influence of the 5-HTTLPR polymorphism and environmental risk factors in a Brazilian sample of patients with autism spectrum disorders. Brain Res 2009;1267:9-17.
- Bradley SL, Dodelzon K, Sandhu HK, Philibert RA. Relationship of serotonin transporter gene polymorphisms and haplotypes to mRNA transcription. Am J Med Genet B Neuropsychiatr Genet 2005;136B:58-61.
- Wu S, Guo Y, Jia M, et al. Lack of evidence for association between the serotonin transporter gene (SLC6A4) polymorphisms and autism in the Chinese trios. Neurosci Lett 2005;381:1-5.
- Ramoz N, Reichert JG, Corwin TE, et al. Lack of evidence for association of the serotonin transporter gene SLC6A4 with autism. Biol Psychiatry 2006;60:186-191
Details
| Primary Language | Turkish |
|---|---|
| Journal Section | Research Article |
| Authors | |
| Publication Date | July 10, 2015 |
| Published in Issue | Year 2015 Volume: 6 Issue: 2 |