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Pilot study on HTR2A promoter polymorphism, -1438G/A (rs6311) and a nearby copy number variation showed association with onset and severity in early onset obsessive-compulsive disorder


Walitza, Susanne; Bové, Daniel Sabanes; Romanos, Marcel; Renner, Tobias; Held, Leonhard; Simons, Michael; Wewetzer, Christoph; Fleischhaker, Christian; Remschmidt, Helmut; Warnke, Andreas; Grünblatt, Edna (2012). Pilot study on HTR2A promoter polymorphism, -1438G/A (rs6311) and a nearby copy number variation showed association with onset and severity in early onset obsessive-compulsive disorder. Journal of Neural Transmission, 119(4):507-515.

Abstract

A previous study showed that a single nucleotide polymorphism (SNP), -1438G/A (rs6311), found in the transcriptional control region of the gene that encodes the serotonin-receptor 2A (HTR2A) was associated with obsessive-compulsive disorder (OCD) in a sample of children and adolescents. In this study, we reanalyzed the association of this SNP with OCD in an enlarged population of 136 cases (55 previous + 81 new cases) and compared them to 106 newly recruited, healthy, age-matched controls. We also investigated whether this SNP or its copy number variations (CNV) was associated with OCD severity and age of onset. The CNV was analyzed in a DNA region located near rs6311. The results confirmed the association between the A-allele and early onset OCD in children and adolescents, with an odds ratio (OR) of 1.69 [95% CI (1.17, 2.46); p = 0.005]. Strikingly, we found that carriers of one copy (deletion) of the CNV were associated with a very early onset OCD (2.5 years earlier than the typical onset), and they had increased CY-BOCS scores (8.7 points higher compared to "normal" CNV and duplications); which is related to increased severity of OCD symptoms (p = 0.031; p = 0.004, respectively). Compared to the normal CNV and duplications, the association between the deletion and OCD showed an OR of 7.56 [95% CI (1.32, 142.84); p = 0.020]. These results pointed to the functional importance of this promoter region of HTR2A; it influenced the occurrence, the onset, and the severity of OCD.

A previous study showed that a single nucleotide polymorphism (SNP), -1438G/A (rs6311), found in the transcriptional control region of the gene that encodes the serotonin-receptor 2A (HTR2A) was associated with obsessive-compulsive disorder (OCD) in a sample of children and adolescents. In this study, we reanalyzed the association of this SNP with OCD in an enlarged population of 136 cases (55 previous + 81 new cases) and compared them to 106 newly recruited, healthy, age-matched controls. We also investigated whether this SNP or its copy number variations (CNV) was associated with OCD severity and age of onset. The CNV was analyzed in a DNA region located near rs6311. The results confirmed the association between the A-allele and early onset OCD in children and adolescents, with an odds ratio (OR) of 1.69 [95% CI (1.17, 2.46); p = 0.005]. Strikingly, we found that carriers of one copy (deletion) of the CNV were associated with a very early onset OCD (2.5 years earlier than the typical onset), and they had increased CY-BOCS scores (8.7 points higher compared to "normal" CNV and duplications); which is related to increased severity of OCD symptoms (p = 0.031; p = 0.004, respectively). Compared to the normal CNV and duplications, the association between the deletion and OCD showed an OR of 7.56 [95% CI (1.32, 142.84); p = 0.020]. These results pointed to the functional importance of this promoter region of HTR2A; it influenced the occurrence, the onset, and the severity of OCD.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Child and Adolescent Psychiatry
04 Faculty of Medicine > Epidemiology, Biostatistics and Prevention Institute (EBPI)
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2012
Deposited On:28 Sep 2011 12:30
Last Modified:05 Apr 2016 15:01
Publisher:Springer
ISSN:0300-9564
Publisher DOI:10.1007/s00702-011-0699-1
PubMed ID:21874579
Permanent URL: http://doi.org/10.5167/uzh-49842

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