Identification of a new variant CYP2D6 allele with a single base deletion in exon 3 and its association with the poor metabolizer phenotype.
Identification of a new variant CYP2D6 allele with a single base deletion in exon 3 and its association with the poor metabolizer phenotype.
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鉴定出外显子 3 中具有单碱基缺失的新变异 CYP2D6 等位基因及其与代谢不良表型的关联。
DOI：
10.1093/hmg/3.6.923
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发表时间：
1994
影响因子：
3.5
通讯作者：
Weiffenbach,B
中科院分区：
文献类型：
--
作者：
Saxena,R;Shaw,GL;Relling,MV;Frame,JN;Moir,DT;Evans,WE;Caporaso,N;Weiffenbach,B
人类CYP 2D 6基因编码异喹胍4-羟化酶，可代谢超过25种重要的治疗药物。不能代谢这些药物，导致“弱代谢者”（PM）表型，在某些情况下，可归因于CYP 2D 6基因中存在先前描述的三种突变中的任一种。为了确定新的等位基因负责PM表型，我们已经检查了CYP 2D 6基因的个人，其表型不符合其表观基因型。DNA测序显示外显子3 T1795中的单碱基缺失，导致移码并在缺失后一个密码子产生终止密码子。我们设计了一种基于PCR的检测方法来检测这个新的等位基因（命名为CYP 2D 6（T）），并对来自肺癌病例对照研究的236名无关个体进行了CYP 2D 6（T）突变的检测。发现8个无关个体携带D 6（T）等位基因。4名受试者还携带非功能性D 6（B）等位基因，这4名D 6（B）/D 6（T）个体的药物代谢表型与D 6（T）等位基因负责降低异喹胍4-羟化酶活性一致。在病例对照研究的高加索对照中，D 6（T）等位基因的频率为1.8%（4/220条染色体）。
The humanCYP2D6gene codes for the enzyme, debrisoquine 4-hydroxylase, which metabolizes over 25 therapeutically important drugs. The inability to metabolize these drugs, which results in a ‘poor metabolizer’ (PM) phenotype, can be attributed, in some cases, to the presence of any of three previously described mutations in theCYP2D6gene. To identify new alleles responsible for the PM phenotype, we have examined theCYP2D6gene from individuals whose phenotypes were not consistent with their apparent genotypes. DNA sequencing revealed a single base deletion in exon 3, T1795, resulting in a frame shift and generating a stop codon one codon after the deletion. A PCR-based test was designed for this new allele (designatedCYP2D6(T)) and 236 unrelated individuals from a lung cancer case control study were tested for the presence of theCYP2D6(T)mutation. Eight unrelated individuals were found to carry theD6(T) allele. Four subjects also carry the non-functionalD6(B)allele and the drug metabolism phenotypes of these fourD6(B)/D6(T)individuals are consistent with theD6(T)allele being responsible for reduced debrisoquine 4-hydroxylase activity. The frequency of the D6(T) allele among Caucasian controls of the case-control study was 1.8% (4/220 chromosomes).
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胰岛素样生长因子 II 基因在成年大鼠中枢神经系统脉络丛和软脑膜中的表达。
DOI：
--
发表时间：
1988
影响因子：
11.1
作者：
F. Stylianopoulou;J. Herbert;M. Soares;A. Efstratiadis
通讯作者：
A. Efstratiadis
影响因子：
64.8
作者：
EDVINSSON, L;DEGUEURCE, A;SCATTON, B
通讯作者：
SCATTON, B
神经生长因子增加新生大鼠纹状体胆碱乙酰转移酶活性。
DOI：
10.1126/science.2861660
发表时间：
1985
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Mobley,WC;Rutkowski,JL;Tennekoon,GI;Buchanan,K;Johnston,MV
通讯作者：
Johnston,MV
成年大鼠小脑浦肯野细胞表达神经生长因子受体免疫反应性：光学显微镜观察
影响因子：
2.9
作者：
E. Pioro;A. Cuello
通讯作者：
A. Cuello
DOI：
10.1073/pnas.83.23.9231
发表时间：
1986-12-01
影响因子：
11.1
作者：
WILLIAMS, LR;VARON, S;GAGE, FH
通讯作者：
GAGE, FH