Influence of HTR3 genetic variability on obsessive-compulsive disorder

Abstract

Purpose

Family, twin, and molecular genetic studies have demonstrated that genetic factors may exert significant influence on the development of OCD and the manifestation of symptoms. Evidence in the extant literature has indicated associations between serotonin-related genetic variants and OCD, but few studies have explored the involvement of serotonin receptor type 3 genes in OCD. The aim of this study was to examine whether HTR3 genetic variants may affect susceptibility to OCD.

Methods

We performed a case-control study with 596 individuals with OCD and 599 controls. Ten common single nucleotide polymorphisms in the five distinct HTR3 genes were genotyped. Single-marker association and haplotype-based association analyses were conducted regarding the affected status and different OCD sub-phenotypes, such as age at onset and clinical symptom dimensions. The impact of HTR3 variants on trait disgust sensitivity was also analyzed.

Results

A significant difference in the genotype distribution of rs1176744 was detected between individuals with OCD and controls (odds ratio (OR) = 0.74, 95% confidence intervals (CI) = 0.60-0.91, p = 0.0041), which was restricted to males when the analyses were stratified by sex (OR = 0.70, CI = 0.54-0.89, p = 0.0039). On analyzing clinical characteristics of OCD, significant associations were found for rs3758987 with age at onset in male subjects (OR = 0.49, CI = 0.30-0.78, p = 0.0025) and for rs6766410 and rs6443930 with the contamination/cleaning dimension in female subjects (OR = 0.36, CI = 0.18-0.69, p = 0.0017 and OR = 0.47, CI = 0.29-0.78, p = 0.0029, respectively). In addition, rs6766410 was significantly related to contamination-based disgust scores in the whole OCD sample (p = 0.0044). A two-marker composite haplotype in HTR3B was associated with OCD in male subjects (OR = 0.75, CI = 0.58-0.97, permutated p = 0.0339)

Conclusions

Our results support a role for common variants of HTR3 in OCD and certain of its clinical phenotypes. These findings may have implications for pharmacogenetic studies of 5-HT3 antagonists in the treatment of OCD.