Evidence of involvement of the human Par-4 (PAWR) gene in major depressive disorder

Abstract

Qbjectives. The aim of the study was to examine the associations between genetic variations in the human PAWR gene and major depressive disorder (MDD) as well as the response to antidepressant treatment. Methods. Six-hundred and two patients with MDD and 543 controls were included in the study; among the MDD patients, 268 were followed-up for a further 8 weeks in order to assess their response to treatment with selective serotonin reuptake inhibitors (SSRIs). Six polymorphisms (rs17005769, rs4842318, rs7305141, rs2307223, rs8176874 and rs2307220) of the PAWR gene were investigated with regard to their association with MDD and antidepressant treatment efficacy. Results. One polymorphism, rs8176874, was in genotypic (uncorrected P = 0.005) and allelic (uncorrected P = 0.0015) association with MDD. Several haplotypes spanning rs7305141–rs2307223–rs8176874 were also significantly associated with MDD after correction for multiple testing (corrected P < 0.05). However, neither single-marker nor haplotype-based analyses suggested an association between the studied markers and SSRI treatment response. Conclusions. Genetic variations in the PAWR gene are related to susceptibility to MDD but not to SSRI treatment response.

Key words::

• Major depressive disorder
• PAWR
• antidepressants
• SSRI
• pharmacogenetic study

Acknowledgements

This work was supported by grants from the National Science Council, Taiwan (NSC 95-2314-B-075-108-MY2, 96-2314-B-075-065-MY2, 97-3112-B-075-005, 98-3112-B-075-005 and 99-3112-B-075-005) and from Taipei Veterans General Hospital, Taiwan (V98C1-055 , V99A-045, V99C1-041 VGHUST98-P1-02 and VGHUST99-P1-01). We would like to thank the National Genotyping Center of the National Research Program for Genomic Medicine, launched by the National Science Council, and Dr. Jer-Yuan Wu of Academia Sinica, Taiwan, for support in the genotyping of samples. The authors report no biomedical financial interests or potential conflicts of interest. No assistance was received in the writing of this manuscript.

Statement of interest

None to declare.