Population genetics of a functional variant of the dopamine beta-hydroxylase gene (DBH).
Population genetics of a functional variant of the dopamine beta-hydroxylase gene (DBH).
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DOI：
10.1002/(sici)1096-8628(19970725)74:4
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发表时间：
1997-07
期刊：
影响因子：
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通讯作者：
J. Cubells;K. Kobayashi;T. Nagatsu;K. Kidd;J. Kidd;F. Calafell;H. Kranzler;H. Ichinose;J. Gelernter
中科院分区：
文献类型：
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作者：
J. Cubells;K. Kobayashi;T. Nagatsu;K. Kidd;J. Kidd;F. Calafell;H. Kranzler;H. Ichinose;J. Gelernter
多巴胺β-羟化酶（E.C. 1.14.17.1;蛋白缩写：DbetaH）催化多巴胺转化为去甲肾上腺素。先前的工作鉴定了编码D β H（基因座符号DBH）的基因的两个表达等位基因，在核苷酸位置910处含有G或T，导致分别由丙氨酸（DBH* 304 A）或丝氨酸（DBH* 304 S）的密码子304指定。目前的研究采用变性梯度凝胶电泳来识别这些等位基因，并在开发了用于快速基因分型的PCR RFLP后，估计了这些等位基因在非洲裔美国人、欧洲裔美国人和几个地理上分散的人群（Mbuti、丹麦人、Adygei、中国人、日本人、Surui、Maya和Nasioi）中的频率。DBH* 304 A是所有测试群体中最常见的等位基因，在每种情况下等位基因频率均大于0.80。不同人群等位基因频率存在显著异质性。DBH* 304 S等位基因在非洲血统的受试者中最常见，在东亚人和北美和南美土著人群中最不常见。DBH* 304 S在非裔美国人中的频率（0.16）显著高于欧裔美国人（0.06; P < 0.004）。在观察到的四个DBH* 304 S纯合子中，所有人都是欧洲人，四个人中有三个是丹麦人。基于经验的P值由计算机模拟，观察到的DBH* 304 S纯合子的比例没有显着不同的Hardy-Weinberg的期望在任何种群后Bonferroni校正多重比较。在不同人群样本中观察到的DBH* 304 S等位基因频率的显著异质性证明了在未来的研究中控制人群分层的重要性，以测试DBH* 304 S与临床表型之间的关联。
Dopamine beta-hydroxylase (E.C. 1.14.17.1; protein abbreviation: DbetaH) catalyzes conversion of dopamine to norepinephrine. Previous work identified two expressed alleles of the gene encoding DbetaH (locus symbol DBH), containing either G or T at nucleotide position 910, resulting in specification by codon 304 of alanine (DBH*304A) or serine (DBH*304S), respectively. The current study employed denaturing gradient gel electrophoresis to identify these alleles, and after developing a PCR RFLP for rapid genotyping, estimated the frequencies of the alleles in African-Americans, European-Americans, and in several geographically dispersed populations (Mbuti, Danes, Adygei, Chinese, Japanese, Surui, Maya, and Nasioi). DBH*304A was the most common allele in all populations tested, with allele frequencies greater than 0.80 in each case. There was significant heterogeneity in allele frequency across population groups. The DBH*304S allele was most common in subjects of African descent, and least common in East Asians and individuals from indigenous populations of North and South America. The frequency of DBH*304S was significantly higher in African-Americans (0.16) than in European-Americans (0.06; P < 0.004). Of the four DBH*304S homozygotes observed, all were Europeans and three of the four were Danes. Based on empirical P-values generated by computer simulation, the observed proportions of DBH*304S homozygotes did not differ significantly from Hardy-Weinberg expectations in any of the populations after Bonferroni correction for multiple comparisons. The observation of significant heterogeneity in DBH*304S allele frequency across different population samples demonstrates the importance of controlling for population stratification in future studies testing for associations between DBH*304S and clinical phenotypes.