Characterization of inter-ethnic genetic variability of CYP2D6, CYP2C19, CYP2B6, NAT2 and GSTs in the Bantu and Nilotic populations of Kenya and implications for the chemotherapy of infectious diseases

Citation:
Oluka MN, Matimba A, Okalebo FA, Osanjo GO, Guantai AN, Masimirembwa CM. "Characterization of inter-ethnic genetic variability of CYP2D6, CYP2C19, CYP2B6, NAT2 and GSTs in the Bantu and Nilotic populations of Kenya and implications for the chemotherapy of infectious diseases." Afr. J. Pharmacol. Ther.. 2014;3(2):38-46.

Abstract:

Background: Drug metabolism genes are variable in populations. African populations are highly genetically
differentiated. Analysis of drug metabolism genes offers opportunities to enhance drug efficacy and reduce toxicity.
Objectives: We characterized SNPs of CYP2D6, CYP2C19, CYP2B6, NAT2 and GST genes in Kenyans.
Methodology: Genotyping of CYP2C19 (*2, *3); CYP2B6 (*6); CYP2D6 (*2,*4, *17, *29); NAT2 (*5, *6, *7, *14); GSTM1 and GSTT1 by PCR-RFLP.
Results: CYP2D6*4 was higher in Eastern Nilotes (9%) compared to Western Nilotes (2.5%) and Bantus (1.7%) (P = 0.002). CYP2D6*17 was higher in Bantus (34%) compared to Nilotes (18 – 23%) (P = 0.003). GSTM1del was higher in Western Nilotes and Bantus (29% -31%) compared to Eastern Nilotes (16%) (P = 0.009). GSTT1del was higher in Eastern Nilotes (41%) compared to Bantus and Western Nilotes (22 - 26%) (P = 0.005). CYP2C19*3 was undetected in Bantus but was >1.0% in Nilotes ((P <0.01). CYP2C19*2 (10 – 18%), CYP2B6*6 (35 – 37%), NAT2*5 (30 – 42%), NAT2*6 (20 – 27%), NAT2*7 (2 – 6%), NAT2*14 (8-14%) were similar in Kenyans. Kenyan frequencies were comparable to other Africans but different from Caucasians and Asians.
Discussion: Variability was evident for CYP2D6*4, CYP2D6*17, GSTM1del and GSTT1del. Findings provide a
framework for Pharmacogenomic optimization of therapeutic outcomes.
Key Words: Pharmacogenomics, Drug metabolism, inter-ethnic variability, Kenyans

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