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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.

Author(s): Lohoff FW(1), Narasimhan S, Rickels K.

Affiliation(s): Author information: (1)1] Psychiatric Pharmacogenetics Laboratory, Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA [2] Mood and Anxiety Disorders Section, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Publication date & source: 2013, Pharmacogenomics J. , 13(5):464-9

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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