Background Some single nucleotide polymorphisms (SNPs) in the cytochrome P450 (CYP)2B6 gene lead to decreased enzyme activity and have an impact on drug metabolism. The present study was designed to investigate the patterns of genetic distinction across a hypervariable region of the CYP2B6 gene, known to contain important SNPs, i.e. rs4803419 and rs3745274, among five major ethnic groups of the Pakistani population. Methods Arlequin v3.5.DnaSPv6.12. and network 5 resources were used to analyze population genetic variance in the partial CYP2B6 gene sequences obtained from 104 human samples belonging to Punjabi, Pathan, Sindhi, Seraiki and Baloch ethnicities of Pakistan. The partial CYP2B6 gene region analyzed in the current study is previously known to possess important SNPs. Results The data analyses revealed that genetic variance among samples mainly came from differentiation within the ethnic groups. However, significant genetic variation was also found among the various ethnic groups. The high pairwise Fst genetic distinction was observed between Seraiki and Sindhi ethnic groups (Fst = 0.13392, P-value = 0.026) as well as between Seraiki and Balochi groups (Fst = 0.04303, P-value = −0.0030). However, the degree of genetic distinction was low between Pathan and Punjabi ethnic groups. Some SNPs, including rs3745274 and rs4803419, which are previously shown in strong association with increased plasma Efavirenz level, were found in high frequency. Besides, a novel SNP, which was not found in dbSNP and Ensemble databases, was identified in the Balochi ethnicity. This novel SNP is predicted to affect the CYP2B6 splicing pattern. Conclusion These results may have significant implications in Pakistani ethnicities in the context of drugs metabolized by CYP2B6, especially in Seraiki and Balochi ethnicity. The novel heterogeneous SNP, found in the present study, might lead to altered drug-metabolizing potential of CYP2B6 and, therefore, may be implicated in non-responder phenomenon.

中文翻译：

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巴基斯坦人群CYP2B6基因部分序列的种族间遗传变异及新变异鉴定

背景 细胞色素 P450 (CYP)2B6 基因中的一些单核苷酸多态性 (SNP) 会导致酶活性降低，并对药物代谢产生影响。本研究旨在调查 CYP2B6 基因高变区的遗传差异模式，该基因已知包含重要的 SNP，即 rs4803419 和 rs3745274，在巴基斯坦人口的五个主要种族中。方法 Arlequin v3.5.DnaSPv6.12。和网络 5 资源用于分析从属于巴基斯坦旁遮普、帕坦、信德、塞拉基和俾路支种族的 104 个人类样本中获得的部分 CYP2B6 基因序列中的群体遗传变异。在当前研究中分析的部分 CYP2B6 基因区域以前已知具有重要的 SNP。结果数据分析表明，样本间的遗传变异主要来自种族内部的差异。然而，在不同种族之间也发现了显着的遗传变异。在 Seraiki 和 Sindhi 族群之间（Fst = 0.13392，P 值 = 0.026）以及 Seraiki 和俾路支族群（Fst = 0.04303，P 值 = -0.0030）之间观察到高成对 Fst 遗传差异。然而，帕坦族和旁遮普族之间的遗传差异程度较低。一些 SNP，包括 rs3745274 和 rs4803419，以前显示与增加的血浆依法韦仑水平密切相关，发现频率很高。此外，在 dbSNP 和 Ensemble 数据库中未发现的一种新的 SNP 在俾路支族中发现。预计这种新型 SNP 会影响 CYP2B6 剪接模式。结论 在 CYP2B6 代谢药物的背景下，这些结果可能对巴基斯坦种族产生重大影响，尤其是在 Seraiki 和 Balochi 种族中。本研究中发现的新型异质 SNP 可能导致 CYP2B6 的药物代谢潜力改变，因此可能与无应答现象有关。