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

J Neural Transm (Vienna). 2012 Apr;119(4):507-15. doi: 10.1007/s00702-011-0699-1. Epub 2011 Aug 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Analysis of Variance
  • Child
  • Child, Preschool
  • DNA Copy Number Variations / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Obsessive-Compulsive Disorder / genetics*
  • Pilot Projects
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic / genetics*
  • Receptor, Serotonin, 5-HT2A / genetics*

Substances

  • Receptor, Serotonin, 5-HT2A