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Association between polymorphisms in catechol-O-methyltransferase (COMT) and cocaine-induced paranoia in European-American and African-American populations.
- Source :
-
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics [Am J Med Genet B Neuropsychiatr Genet] 2011 Sep; Vol. 156B (6), pp. 651-60. Date of Electronic Publication: 2011 Jun 08. - Publication Year :
- 2011
-
Abstract
- Catechol-O-methyltransferase (genetic locus, COMT) is a major enzyme involved in catecholamine metabolism and has been associated with numerous psychiatric phenotypes. We studied COMT SNPs and haplotypes in cocaine-induced paranoia (CIP) in African-American (AA) and European-American (EA) populations. We genotyped 17 SNPs across the COMT locus in 319 AA pedigrees (848 individuals) and 302 EA pedigrees (707 individuals). Family-controlled association analyses were conducted using FBAT. We found SNP rs737865 to be nominally significantly associated in the AA family population (P = 0.05). In EAs, the best-known marker, rs4680 (Val158Met), was nominally significant in additive models (P = 0.03). SNP rs174696 also showed nominal significance in additive models (P = 0.02). We considered the three SNPs (rs737866-rs4680-rs174696) together in haplotype analysis in both family populations, using HBAT. The A-A-T haplotype was significantly associated with CIP in EAs (Z = 2.845; P = 0.0044, global P = 0.020). We then studied COMT SNPs in an additional 738 AA and 404 EA unrelated cocaine dependent individuals with and without paranoia. The A-A-T haplotype was significantly associated to CIP in the AA unrelated population (P = 0.0015). Two haplotypes, A-G-C and A-A-C, were significant in the EA unrelated population (P = 0.001 and 0.0003). We also identified rs4680 and three other SNPs, rs933271, rs5993883, and rs740603, as potentially functional variants, as predicted by a signature of positive selection in unrelated EAs and AAs. Based on our robust family-controlled and unrelated-affected analyses, we conclude that COMT is associated with CIP, possibly as a result of its role in the metabolism of dopamine and norepinephrine.<br /> (Copyright © 2011 Wiley-Liss, Inc.)
- Subjects :
- Case-Control Studies
Cocaine pharmacology
Dopamine metabolism
Female
Genetic Predisposition to Disease
Genotype
Humans
Male
Norepinephrine metabolism
Black or African American genetics
Catechol O-Methyltransferase genetics
Cocaine-Related Disorders genetics
Paranoid Disorders chemically induced
Paranoid Disorders genetics
Polymorphism, Single Nucleotide
White People genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1552-485X
- Volume :
- 156B
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 21656904
- Full Text :
- https://doi.org/10.1002/ajmg.b.31205