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Transl Psychiatry. 2015 Jul 28;5:e608. doi: 10.1038/tp.2015.97.

A double amino-acid change in the HLA-A peptide-binding groove is associated with response to psychotropic treatment in patients with schizophrenia.

Author information

1
201;quipe EA4627, Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France.
2
1] INSERM, U955, Psychiatrie Génétique, Créteil, France [2] Université Paris-Est, Faculté de Médecine, Créteil, France [3] AP-HP, DHU PePSY, Pôle de Psychiatrie, Hôpitaux Universitaires Henri Mondor, Créteil, France [4] Fondation FondaMental, Créteil, France.
3
1] Fondation FondaMental, Créteil, France [2] Service de Psychiatrie Adulte, Hôpital Gabriel Montpied, Clermont-Ferrand, France.
4
INSERM, U775, Centre de recherches Biomédicales, Université Paris Descartes, Paris, France.
5
INSERM, U955, Psychiatrie Génétique, Créteil, France.
6
1] INSERM, U955, Psychiatrie Génétique, Créteil, France [2] Université Paris-Est, Faculté de Médecine, Créteil, France [3] Fondation FondaMental, Créteil, France.
7
1] Laboratoire Jean Dausset (LabEx Transplantex) et INSERM, U1160, Hôpital Saint Louis, Paris, France [2] Université Paris Diderot, Sorbonne Paris-Cité, Paris, France.

Abstract

The choice of an efficient psychotropic treatment for patients with schizophrenia is a key issue to improve prognosis and quality of life and to decrease the related burden and costs. As for other complex disorders, response to drugs in schizophrenia is highly heterogeneous and the underlying molecular mechanisms of this diversity are still poorly understood. In a carefully followed-up cohort of schizophrenic patients prospectively treated with risperidone or olanzapine, we used a specially designed single-nucleotide polymorphism (SNP) array to perform a large-scale genomic analysis and identify genetic variants associated with response to psychotropic drugs. We found significant associations between response to treatment defined by the reduction in psychotic symptomatology 42 days after the beginning of treatment and SNPs located in the chromosome 6, which houses the human leukocyte antigen (HLA). After imputation of the conventional HLA class I and class II alleles, as well as the amino-acid variants, we observed a striking association between a better response to treatment and a double amino-acid variant at positions 62 and 66 of the peptide-binding groove of the HLA-A molecule. These results support the current notion that schizophrenia may have immune-inflammatory underpinnings and may contribute to pave the way for personalized treatments in schizophrenia.

PMID:
26218850
PMCID:
PMC5068718
DOI:
10.1038/tp.2015.97
[Indexed for MEDLINE]
Free PMC Article

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