No association between anxiety disorders and catechol-O-methyltransferase polymorphism

Ohara, Koichi; Nagai, Miho; Suzuki, Yasuo; Ochiai, Masato; Ohara, Kenshiro

doi:10.1016/s0165-1781(98)00062-6

Cited by 95 publications

(60 citation statements)

References 15 publications

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“…In contrast to our findings of the Val158Met variant are the results of two Asian studies (Ohara et al, 1998;Woo et al, 2004). Ohara et al (1998) investigated a sample of anxiety disorder patients (n ¼ 108) including a small number of PD patients (n ¼ 29) and found no association.…”

Section: Discussioncontrasting

confidence: 99%

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

Rothe

Koszycki

Bradwejn

et al. 2006

Neuropsychopharmacol

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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.

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Section: Discussioncontrasting

confidence: 99%

“…Ohara et al (1998) investigated a sample of anxiety disorder patients (n ¼ 108) including a small number of PD patients (n ¼ 29) and found no association. This small sample of PD patients had very low power to detect the COMT effect sizes observed in our study as well as in Domschke et al (2004) and Hamilton et al (2002).…”

Section: Discussionmentioning

confidence: 99%

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

Rothe

Koszycki

Bradwejn

et al. 2006

Neuropsychopharmacol

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“…It has also been strongly associated with one anxiety disorder in particularFpanic disorder ( (Ohara et al, 1998;Samochowiec et al, 2004) and, according to a recent meta-analysis, not with obsessive-compulsive disorder (Azzam and Mathews, 2003). There was therefore ample a priori reason to hypothesize that we would find an effect of the val158met polymorphism on neuroticism and extraversion in this study.…”

Section: Discussionmentioning

confidence: 56%

“…When looking at patients with panic disorder, four of five association studies (one of which also provided evidence of linkage; Hamilton et al, 2002) have implicated COMT as a probable risk locus (Domschke et al, 2004;Hamilton et al, 2002;Ohara et al, 1998;Woo et al, 2002Woo et al, , 2004. Thus, the bulk of the published data implicate the COMT gene or a nearby region as a susceptibility locus for panic disorder and other anxiety-related traits, although the specific site(s) within the gene that confer this susceptibility, and the apparent sex-specific effects (in some studies), remain to be established.…”

Section: Introductionmentioning

confidence: 99%

COMT Polymorphisms and Anxiety-Related Personality Traits

Stein

Fallin

Schork

2005

Neuropsychopharmacol

198

128

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High neuroticism and low extraversion are characteristic of anxiety-prone individuals. A functional variant in the catechol-Omethyltransferase (COMT) gene, the Val158Met ('val/met') polymorphism, has been associated in some prior studies with several phenotypes, including neuroticism. We tested the hypothesis that the val158met polymorphism would be associated with both high neuroticism and low extraversion, making it a plausible candidate locus for anxiety susceptibility. To determine whether val158met is responsible for these effects, we also evaluated the association with haplotypes that included two other SNPs within the COMT gene. We collected a sample of 497 undergraduate college students who were phenotyped on a personality inventory (the NEO-Personality Inventory-Raised (NEO-PI-R)). Subjects were genotyped for three COMT polymorphisms: the well-studied nonsynonymous SNP rs4680 that generates a valine-to-methionine substitution (val158met), rs737865 (near exon #1), and rs165599 (also functional, near the 3 0 -UTR). Together, these three SNPs define a haplotype that is associated with reduced COMT expression in human brain. Logistic regression analyses were used to examine the effects of individual SNPs on extraversion and neuroticism scores. Score tests for association between these traits (quantitatively and dichotomously considered) and haplotypes were also conducted. We evaluated potential for population stratification artifact by genotyping a set of 36 unlinked highly polymorphic markers previously demonstrated to distinguish sufficiently ancestry of major American populations. Two of the SNPs (rs4680 ('val/met') and rs737865) were significantly associated with (low) extraversion and, less consistently, with (high) neuroticism, with effects confined to women. A significant association between COMT haplotype and (low) extraversion and (high) neuroticism was also observed. Formal testing showed that population structure did not explain the findings. These data suggest that involvement of the COMT locus in susceptibility to anxiety-related traits (ie low extraversion and high neuroticism) is unlikely to be wholly accounted for by the well-studied rs4680 ('val/met') polymorphism. Other functional variants may exist that contribute to this relationship. Possible sex-specific effects remain to be further studied and explained.

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“…The GYA transition in codon 158 of the COMT gene results in a valine to methionine substitution and is associated with a three-to fourfold decrease in enzyme activity (valine = high-activity, methionine = low-activity) (Lotta et al, 1995). It has already been reported by Karayiourgou et al (1997) that the lowactivity COMT (COMT L) allele occurs significantly more frequently in male OCD patients, but opposing results have also been obtained (Erdal et al, 2003;Karayiorgou et al, 1999;Ohara et al, 1998). In addition, one might theorize that lower densities of the D 2 receptor in OCD patients are caused by genetic factors.…”

Section: Introductionmentioning

confidence: 99%

Association between the dopamine D2 receptor TaqI A2 allele and low activity COMT allele with obsessive–compulsive disorder in males

Denys

Nieuwerburgh

Deforce

et al. 2006

European Neuropsychopharmacology

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Background: Mounting evidence suggests the involvement of the dopamine system in the pathophysiology of obsessive-compulsive disorder. Method: The relationship of the dopamine D 2 receptor (DRD2) TaqI A, and catechol-O-methyltransferase (COMT) NlaIII High/Low activity polymorphism to obsessive-compulsive disorder (OCD) was examined in a sample of 150 patients and 150 controls. Results: OCD patients did not show significant differences in genotype distribution and allele frequency for polymorphisms investigated relative to controls. However, when the sample was stratified by gender, there was a trend to a significant predominance of the DRD2 A2A2 genotype ( p = 0.049), and a higher frequency of the DRD2 A2 allele ( p = 0.020) and low-activity COMT allele ( p = 0.035) in male OCD patients compared to male controls. In addition, we observed an association of the DRD2 A2A2 genotype in patients with an early onset of disease (V15 years) ( p = 0.033). Conclusions: Our findings replicate previous reports and provide support for a potential role of the COMT and DRD2 locus in subgroup of male, early onset patients with OCD.

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No association between anxiety disorders and catechol-O-methyltransferase polymorphism

Cited by 95 publications

References 15 publications

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

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

COMT Polymorphisms and Anxiety-Related Personality Traits

Association between the dopamine D2 receptor TaqI A2 allele and low activity COMT allele with obsessive–compulsive disorder in males

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