title: Haplotype-controlled analysis of the association of a non-synonymous single nucleotide polymorphism at DBH (+ 1603C --> T) with plasma dopamine beta-hydroxylase activity.
abstract: The DBH locus controls plasma dopamine beta-hydroxylase activity (pDbetaH). A 5'-upstream single nucleotide polymorphism (SNP) at DBH (-1021C --> T) explains approximately 45% of the variance in pDbetaH, and a non-synonymous SNP in exon 11 (+ 1603C --> T) an additional 2%. However, that regression result underestimates the effect of + 1603C --> T because of its low minor allele frequency. We estimated the biological effect of + 1603C --> T on pDbetaH by comparing subjects of identical -1021CgammaT genotype, in a diagnostically heterogeneous group of subjects of European origin (N = 367). + 1603C --> T genotype associated with pDbetaH within groups of identical genotype at -1021 C --> T, accounting for 5%-16% of the variance. There was no significant linkage disequilibrium between -1021C --> T and + 1603C --> T (D = 0.0058, D' = 0.4774, d(2) = 0.0011, P > 0.05), confirming the validity of assessing the two polymorphisms independently. These results suggest that altered homospecific activity of the enzyme can contribute to variation in pDbetaH. This conclusion informs how associations between DBH and psychiatric disorders should be approached. (c) 2005 Wiley-Liss, Inc.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine and VA Connecticut Healthcare System, West Haven, Connecticut.
authors.forename: Yilang
authors.initials: Y
authors.lastname: Tang
authors.forename: George M
authors.initials: GM
authors.lastname: Anderson
authors.forename: Cyrus P
authors.initials: CP
authors.lastname: Zabetian
authors.forename: Michael D
authors.initials: MD
authors.lastname: Köhnke
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Cubells
mesh_terms: D000328:Adult; D004299:Dopamine beta-Hydroxylase / Q000097:blood* / Q000235:genetics*; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: D004299:Dopamine beta-Hydroxylase