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

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