POPULATION-GENETICS OF A FUNCTIONAL VARIANT OF THE DOPAMINE-BETA-HYDROXYLASE GENE (DBH)

Dopamine beta-hydroxylase (E.C. 1.14.17.1; protein abbreviation: D bet a H) catalyzes conversion of dopamine to norepinephrine. Previous work identified two expressed alleles of the gene encoding D beta H (locus symbol DBH), containing either G or T at nucleotide position 910, res ulting in specification by codon 304 of alanine (DBH304A) or serine ( DBH304S), respectively, The current study employed denaturing gradien t gel electrophoresis to identify these alleles, and after developing a PCR RFLP for rapid genotyping, estimated the frequencies of the alle les in African-Americans, European-Americans, and in several geographi cally dispersed populations (Mbuti, Danes, Adygei, Chinese, Japanese, Surui, Maya, and Nasioi). DBH304A was the most common allele in all p opulations tested, with allele frequencies greater than 0.80 in each c ase, There was significant heterogeneity in allele frequency across po pulation groups, The DBH304S allele was most common in subjects of Af rican descent, and least common in East Asians and individuals from in digenous populations of North and South America, The frequency of DBH 304S was significantly higher in African-Americans (0.16) than in Euro pean-Americans (0.06; P < 0.004), Of the four DBH304S homozygotes obs erved, all were Europeans and three of the four were Danes, Based on e mpirical P-values generated by computer simulation, the observed propo rtions of DBH304S homozygotes did not differ significantly from Hardy -Weinberg expectations in any of the populations after Bonferroni corr ection for multiple comparisons, The observation of significant hetero geneity in DBH304S allele frequency across different population sampl es demonstrates the importance of controlling for population stratific ation in future studies testing for associations between DBH304S and clinical phenotypes. (C) 1997 Wiley-Liss, Inc.