Association Study Of HTR3A Gene With Response To Risperidone Treatment In Chinese Schizophrenia Patients

Schizophrenia (MIM 181500) is one of the most severe mental disorders affecting approximately 1% of the population with life-long devastating consequences. Lots of family, twin and adoption studies have demonstrated the role of genetic components and environmental factors in the aetiology of schizophrenia. Although great efforts have been put into the genetic studies in schizophrenia, major common risk genes and inheritance pattern in this disease have not been found consistently. Obviously, this inheritance pattern is very complicated and is non-Mendelian. Through linkage analysis and association analysis, many candidate chromosome regions and risk genes for schizophrenia have been identified. Additionally, the achievement in molecular neuropathology, neurophysiology, in vivo brain imaging, and psychopharmacology implied that that schizophrenia may be a neurodevelopmental and progressive disorder involving the abnormalities of dopaminergic, serotonin, glutamate, and aminobutyric acidergic systems.In the therapy of schizophrenia, we are also facing a great challenge, since the therapeutic responses to antipsychotic medication, including resperidone, are significantly variable.The suggestion of 5-hydroxytryptamine (serotonin) involvement in schizophrenia was first made in the mid-1950s, with serotonic deficiency being detected in schizophrenic patients. Since then, many researches focused on the relationship between the genes of components of serotonic system and schizophrenia or therapeutic response to antipsychotic medication. However, to our knowledge, no research has examined the association between therapeutic response to resperidone and HTR3A gene, the gene of the receptor which is the only ionotropic ligand-gated ion channel in serotonic system. Moreover, some researches showed the association between HTR3A gene and schizophrenia. Thus, we performed an association study based on unrelated drug-naive Chinese schizophrenic patients treated with risperidone. Statistical analysis revealed association between genotypes of g.14396A>G polymorphism and score reductions of negative and general subscales after adjusting for the influence of the baseline scores of each subscale (P (F, df)=0.026(3.763,2), 0.023 (3.937,2) respectively). One haplotype, C-A-G, contributed to an effective response in general symptoms (X~2=7.3, P=0.007, Odd ratio=3.371).In addition, our study discussed the disadvantages of the commonly used criterion for responder or non-responder group separation and gave some suggestions for improvement.