Lachman HM, Morrow B, Shprintzen R, Veit S, Parsia SS, Faedda G et al. Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome. Am J Med Genet 67: 468-472

Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
American Journal of Medical Genetics (Impact Factor: 3.23). 09/1996; 67(5):468-72. DOI: 10.1002/(SICI)1096-8628(19960920)67:5<468::AID-AJMG5>3.0.CO;2-G
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Velo-cardio-facial-syndrome (VCFS) is a common congenital disorder associated with typical facial appearance, cleft palate, cardiac defects, and learning disabilities. The majority of patients have an interstitial deletion on chromosome 22q11. In addition to physical abnormalities, a variety of psychiatric illnesses have been reported in patients with VCFS, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. The psychiatric manifestations of VCFS could be due to haploin-sufficiency of a gene(s) within 22q11. One candidate that has been mapped to this region is catechol-O-methyltransferase (COMT). We recently identified a polymorphism in the COMT gene that leads to a valine-->methionine substitution at amino acid 158 of the membrane-bound form of the enzyme. Homozygosity for COMT158met leads to a 3-4-fold reduction in enzymatic activity, compared with homozygotes for COMT158val. We now report that in a population of patients with VCFS, there is an apparent association between the low-activity allele, COMT158met, and the development of bipolar spectrum disorder, and in particular, a rapid-cycling form.

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    • "Notably, the 22q11.2 locus includes the catechol-O-methyltransferase (COMT) gene, which codes for an enzyme involved in prefrontal dopamine metabolism (Egan et al., 2001; Fallgatter and Lesch, 2007; Gothelf et al., 2007; Lachman et al., 1996) which may be relevant to behavioral manifestations of inattention and impulsivity in 22q11DS (Cole et al., 2013; Cools et al., 2007; Gothelf et al., 2007; Shashi et al., 2006; Soeiro-De-Souza et al., 2013). Investigation of the relationships between impulsive behavior, response inhibition-related neural circuitry, and allelic variation and expression of COMT and other genes involved in dopaminergic function is warranted in future, larger-scale studies of this syndrome. "

    Clinical neuroimaging 08/2015; 9:310-321. DOI:10.1016/j.nicl.2015.08.006 · 2.53 Impact Factor
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    • "We focused on this single nucleotide polymorphism, as it is the most established and widely studied functional mutation in the COMT gene (Chen et al. 2004; Scheggia et al. 2012). Future investigations with larger samples size would be required to assess the potential effects played by other COMT functional polymorphisms/ haplotypes (Lachman et al. 1996; Bray et al. 2003; Meyer-Lindenberg et al. 2006; Nackley et al. 2006; Gothelf et al. 2014). Written, informed consent was obtained from all subjects participating in the study, which was approved by the local ethics committee at the Santa Lucia Foundation of Rome. "

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    • "The COMT gene, mapped to chromosome 22q11, encodes catechol- O-methyltransferase, the enzyme that catalyzes the degradation of catecholamines and the methylation of catechol estrogens, an important mechanism for inactivating estrogen [10]. The COMT gene exhibits a functional single nucleotide polymorphism (SNP) (rs4680) due to a G to A transition that results in an amino acid change from valine to methionine at codon 158 (Val158Met) [11]. A different COMT activity is associated with this polymorphism, since the enzyme activity of the Met/ Met genotype is one quarter of that observed in the Val/Val genotype, and heterozygous subjects exhibit intermediate enzyme activity [12]. "
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    ABSTRACT: The greater predisposition of women to Alzheimer's disease (AD), owing to the decrease in postmenopausal estrogen, may be influenced by polymorphic variation in genes regulating estrogen metabolism (e.g., COMT) and estrogen biosynthesis (e.g., CYP17). In order to better understand how the estrogen pathway genetic variation might affect AD onset, we conducted a case-control study of two single nucleotide polymorphisms (SNPs) of these two genes (COMT rs4680 and CYP17 rs743572) in a sample of AD patients of Italian origin. The COMT allele and genotype were found associated neither with AD onset nor with parameters of AD severity, such as cognitive impairment, age at onset, or disease duration. In contrast, CYP17 was found to affect the age at disease onset mainly in males and, as compared with noncarriers, people carrying the A2 (C) allele had a 2.2-fold increased risk for AD. These findings suggest that the CYP17 A2 allele influences AD susceptibility in a sex-specific way by acting not only on AD risk but also on the age at disease onset, an important parameter of AD severity.
    Journal of the Neurological Sciences 06/2014; 344(1-2). DOI:10.1016/j.jns.2014.06.045 · 2.47 Impact Factor
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