Interaction between polymorphisms in serotonin transporter (SLC6A4) and serotonin receptor 2A (HTR2A) genes predict treatment response to venlafaxine XR in generalized anxiety disorder.
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.
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.
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D000928:Antidepressive Agents / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000235:genetics*; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D003511:Cyclohexanols / Q000627:therapeutic use*; D004311:Double-Blind Method; D006239:Haplotypes; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D000069470:Venlafaxine Hydrochloride; D044465:White People / Q000235:genetics
D000928:Antidepressive Agents; D054316:Biomarkers, Pharmacological; D003511:Cyclohexanols; D044402:Receptor, Serotonin, 5-HT2A; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D000069470:Venlafaxine Hydrochloride