Inter-ethnic genetic variations and novel variant identification in the partial sequences of gene in Pakistani population.

Background: Some single nucleotide polymorphisms (SNPs) in the cytochrome P450 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 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 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, -value = 0.026) as well as between Seraiki and Balochi groups (Fst = 0.04303, -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 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 and, therefore, may be implicated in non-responder phenomenon.