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Interaction between polymorphisms in serotonin transporter (SLC6A4) and serotonin receptor 2A (HTR2A) genes predict treatment response to venlafaxine XR in generalized anxiety disorder

The Pharmacogenomics Journal volume 13, pages 464–469 (2013)Cite this article

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Abstract

Variation in genes involved in serotonergic signaling is thought to be associated with antidepressant treatment response in generalized anxiety disorder (GAD). We examined a possible interaction between the serotonin transporter gene (SLC6A4) 5-HTTLPR/rs25531 haplotype and the serotonin 2A receptor gene (HTR2A) single-nucleotide polymorphism (SNP) rs7997012 in antidepressant treatment outcome in GAD. Patients diagnosed with GAD received venlafaxine XR treatment as part of an 18-month relapse prevention study. Genotypes obtained for the 5-HTTLPR/rs25531 (La/La, La/S or S/S) haplotype and rs7997012 SNP (G or A) in the European American population (n=112) were used for pharmacogenetic analysis. Our data show that subjects with genotypes La/La+G/G or La/La+G/A (n=28) had significantly lower Hamilton Anxiety Scale (HAM-A) scores than those with genotypes La/S+A/A or S/S+A/A (n=12) at 6 months (HAM-A difference=10.7; P<0.0001). Single-marker analysis only showed HAM-A differences of 4.3 (5-HTTLPR/rs25531: La/La versus La/S+S/S) and 4.8 (rs7997012: G/G+G/A versus A/A), showing for the first time a significant gene–gene interaction between these markers.

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Acknowledgements

This research was supported by the US Public Health Research grant MH065963 (KR) and K08MH080372 (FWL). The data for this study were collected between 2005 and 2009. We thank the Wyeth Laboratories for providing all study medication. The study was registered under clinical trials.gov. Identifier: NCT00183274.

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Authors and Affiliations

  1. Department of Psychiatry, Psychiatric Pharmacogenetics Laboratory, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    F W Lohoff & S Narasimhan

  2. Department of Psychiatry, Mood and Anxiety Disorders Section, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    F W Lohoff & K Rickels

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Correspondence to F W Lohoff.

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Lohoff, F., Narasimhan, S. & Rickels, K. Interaction between polymorphisms in serotonin transporter (SLC6A4) and serotonin receptor 2A (HTR2A) genes predict treatment response to venlafaxine XR in generalized anxiety disorder. Pharmacogenomics J 13, 464–469 (2013). https://doi.org/10.1038/tpj.2012.33

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