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古巴人和尼加拉瓜人的 CYP2D6 基因型和去甲异喹胍羟化表型。

CYP2D6 genotype and debrisoquine hydroxylation phenotype in Cubans and Nicaraguans.

机构信息

CICAB-CAIBER Centro de Investigación Clínica, Hospital Universitario Servicio Extremeño de Salud SES, Facultad de Medicina Universidad de Extremadura, Badajoz, Spain.

出版信息

Pharmacogenomics J. 2012 Apr;12(2):176-83. doi: 10.1038/tpj.2010.85. Epub 2010 Dec 7.

DOI:10.1038/tpj.2010.85
PMID:21135868
Abstract

CYP2D6 genotype and debrisoquine metabolic ratio (MR) were analyzed in 133 Nicaraguan Mestizos (NMs) and 260 Cubans divided into Cuban Mestizos (CMs) and White Cubans (WCs). The frequencies of poor metabolizers (MR12.6) were 6% in NMs, 3.9% in CMs and 5.3% in WCs. The frequencies of ultrarapid metabolizers (MR0.1) were 0% in NMs, 2.3% in CMs and 5.3% in WCs. Mean (±s.d.) MR among extensive metabolizers (MR<12.6) was higher in NMs (1.5±1.6; n=118) than in CMs (1.0±1.3; n=124; P<0.001) and WCs (0.7±1.0; n=124; P<0.001). MR correlated with the 'activity score' of CYP2D6 genotypes (P<0.05; r=-0.55). Mean MR was higher among NMs than WCs and CMs for groups classified as 1 (P<0.05) or 2 (P<0.01) 'activity score'. In addition, mean (±s.d.) MR was higher among subjects carrying CYP2D617 than in CYP2D6 wt/wt (P<0.001). The CYP2D610 allele was higher in NMs (3.1%) than in CMs (0.8%; P<0.05) and WCs (0.4%; P<0.05). CYP2D617 allele was higher in CMs (10.2%) than WC (2.7%; P<0.005) and NMs (0%). Thus, the variability in CYP2D6 phenotypes found may be related to differences in allele frequency among groups (that is, CYP2D610 and *17 highest in NMs and CMs, respectively). However, the influence of environmental factors or alleles different than those studied here cannot be ruled out.

摘要

在 133 名尼加拉瓜梅斯蒂索人(NMs)和 260 名古巴人中分析了 CYP2D6 基因型和去甲替林代谢比(MR),这些古巴人分为古巴梅斯蒂索人(CMs)和白古巴人(WCs)。不良代谢者(MR>12.6)的频率分别为 6%、3.9%和 5.3%。超快代谢者(MR<0.1)的频率分别为 0%、2.3%和 5.3%。广泛代谢者(MR<12.6)的平均(±s.d.)MR 在 NMs 中更高(1.5±1.6;n=118),而在 CMs 中更低(1.0±1.3;n=124;P<0.001),在 WCs 中更低(0.7±1.0;n=124;P<0.001)。MR 与 CYP2D6 基因型的“活性评分”相关(P<0.05;r=-0.55)。根据“活性评分”分类,NMs 的 MR 高于 WCs 和 CMs 的组分别为 1(P<0.05)或 2(P<0.01)。此外,携带 CYP2D617 的个体的平均(±s.d.)MR 高于 CYP2D6 wt/wt(P<0.001)。CYP2D610 等位基因在 NMs(3.1%)中的频率高于 CMs(0.8%;P<0.05)和 WCs(0.4%;P<0.05)。CYP2D617 等位基因在 CMs(10.2%)中的频率高于 WCs(2.7%;P<0.005)和 NMs(0%)。因此,发现的 CYP2D6 表型的变异性可能与群体中等位基因频率的差异有关(即 CYP2D610 和*17 在 NMs 和 CMs 中最高)。然而,不能排除环境因素或除研究外的等位基因的影响。

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