Association of the Val158Met Catechol O-Methyltransferase Genetic Polymorphism with Panic Disorder

Abstract

Genetic as well as clinical data suggest that catechol O-methyltransferase (COMT) is involved in multiple complex psychiatric conditions. Recent studies have described an association between the Val158Met COMT polymorphism and panic disorder. Other recent investigations provide evidence that there are other loci within or nearby the COMT gene that may contribute to the susceptibility to panic disorder. To further evaluate the influence of the Val158Met COMT polymorphism in panic disorder we genotyped this marker in the coding region of the COMT gene and two additional variants (rs737865 and rs165599) in the 5 0 and the 3 0 region, respectively, in two independent Canadian samples: 121 nuclear families, and 89 cases with matched controls. In the nuclear families, significant transmission disequilibrium for the valine allele was observed between the alleles of the Val158Met COMT polymorphism and panic disorder (po0.01). A significant excess of the valine allele was found in analysis of the case-control sample (po0.01). This effect was mainly derived from the subgroup of females. This finding, including the female effect, replicates earlier results in studies of the Val158Met polymorphism in panic disorder. No significant results were found for the other two markers. These results support the hypothesis that the valine allele of the Val158Met COMT polymorphism or a nearby locus is involved in the etiopathogenesis of panic disorder.

Catechol-O-Methyltransferase (COMT): A Gene Contributing to Sex Differences in Brain Function, and to Sexual Dimorphism in the Predisposition to Psychiatric Disorders

“…This finding is the latest in a line of studies that show relationships between COMT genotype and personality traits in women but not in men. In particular, anxietyrelated phenotypes (such as harm avoidance or neuroticism) have been repeatedly (though often weakly) associated in women with the Met 158 allele (Eley et al, 2003;Enoch et al, 2003;Olsson et al, 2005;Stein et al, 2005), with similar findings in anxiety disorder (Domschke et al, 2004;Woo et al, 2004;Rothe et al, 2006). A recent meta-analysis of the panic disorder studies (Domschke et al, 2007) confirmed this sex difference, but also revealed an additional complexity, in that the relationship interacted with ethnicity such that panic disorder was associated with the Met 158 allele in Caucasian women but with the Val 158 allele in Asian women.…”

Large-Scale Evaluation of Genetic Variants in Candidate Genes for Colorectal Cancer Risk in the Nurses' Health Study and the Health Professionals' Follow-up Study

“…Table 3 presents the main effects for 43 SNPs with a P trend < 0.05 but P trend > 0.01. Of interest is the functional nonsynonymous polymorphism catechol-O-methyltransferase (COMT) Val 158 Met involved in the dopaminergic pathway and associated with several psychiatric conditions (16), which in this study was associated with a reduced risk of colorectal cancer (OR, 0.75 and 0.58 for the heterozygote and minor allele variant, respectively).…”

Genetic variability in estrogen disposition: Potential clinical implications for neuropsychiatric disorders

“…Few studies have observed association of intermediate phenotypes of anxiety mainly harm avoidance [Enoch et al, 2003], low extraversion, and high neuroticism [Eley et al, 2003;Stein et al, 2005] in women with low activity Met allele. In contrast, women with phobic anxiety [McGrath et al, 2004] and panic disorder [Rothe et al, 2006] showed significant over-representation of Val allele. Women specific influence of COMT gene variation has also been reported for other loci in the gene.…”