TABLE 1.
Characteristics and minor allele frequency (MAF) of the 70 single nucleotide polymorphisms (SNPs) detected in the Zimbabwean subjects. Each SNP had a MAF > 5%, and the predicted and reported functional changes of each cytochrome P450 (CYP) were described.
| DNA strand | Enzyme | Identifier | Allele | MAF (%) | Chromosome position | Nucleotide change | Amino acid change | SIFT/GWAVA prediction | Reported enzyme activity | Variant consequence | Region | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EXP | AFR | ZIM | EUR | |||||||||||
| 1 | CYP1A2 | rs2069514 | CYP1A2*1C | 29.39 | 31.32 | — | 1.99* | 74745879 | G > A | — | -/DEL | Decreased (Nakajima et al., 1999) | Upstream Gene | — |
| rs762551 | CYP1A2*1F | 53.51 | 56.2 | 57 | 67.99** | 74749576 | C > A | — | -/DEL | Increased (Lu et al., 2020) | Intron | I1 | ||
| rs2069526 | CYP1A2*1K | 11.84 | 12.33 | — | 2.39* | 74749000 | T > G | — | -/TOL | Decreased (Al-Ahmad et al., 2017) | Intron | I1 | ||
| NOVEL_74753482 | Novel-1 | 12.72 | — | — | — | 74753482 | G > A | — | -/TOL | — | Intron | I6 | ||
| NOVEL_74753485 | Novel-2 | 86.84 | — | — | — | 74753485 | G > C | — | -/TOL | — | Intron | I6 | ||
| NOVEL_74753512 | Novel-3 | 13.16 | — | — | — | 74753512 | C > T | — | -/TOL | — | Intron | I6 | ||
| NOVEL_74753515 | Novel-4 | 7.02 | — | — | — | 74753515 | G > A | — | -/TOL | — | Intron | I6 | ||
| NOVEL_74747828 | Novel-5 | 8.33 | — | — | — | 74747828 | C > T | — | -/DEL | — | Upstream Gene | - | ||
| NOVEL_74747713 | Novel-6 | 6.14 | — | — | — | 74747713 | A > G | — | -/DEL | — | Upstream Gene | - | ||
| NOVEL_74747716 | Novel-7 | 7.46 | — | — | — | 74747716 | C > T | — | -/DEL | — | Upstream Gene | - | ||
| NOVEL_74747757 | Novel-8 | 10.09 | — | — | — | 74747757 | G > A | — | -/DEL | — | Upstream Gene | - | ||
| rs1022705765 | rs1022705765 | 10.53 | 0* | — | — | 74753493 | G > A | — | -/TOL | — | Intron | I6 | ||
| rs1450415112 | rs1450415112 | 9.65 | 0* | — | — | 74753511 | A > G | — | -/TOL | — | Intron | I6 | ||
| rs951840747 | rs951840747 | 10.09 | 0* | — | — | 74753480 | C > T | — | -/TOL | — | Intron | I6 | ||
| CYP2C9 | rs2256871 | CYP2C9*9 | 14.04 | 8.17 | 13 | 0.1* | 94949217 | A > G | His251Arg | DEL/DEL | Normal (Matimba et al., 2009) | Missense | E5 | |
| NOVEL_94956743 | Novel-9 | 7.46 | - | — | — | 94956743 | T > C | — | -/TOL | — | Intron | I5 | ||
| NOVEL_94977838 | Novel-10 | 6.14 | - | — | — | 94977838 | C > T | — | -/TOL | — | Intron | I6 | ||
| rs2017319 | rs2017319 | 13.60 | 12.03 | 10 | 0.2* | 94988878 | C > T | Ala441 (3D) | -/TOL | — | Synonymous | E9 | ||
| rs75541073 | rs75541073 | 16.23 | 19.14 | — | 0.1* | 94948233 | G > A | — | -/TOL | — | Intron | I4 | ||
| rs9332127 | rs9332127 | 14.47 | 15.81 | — | 0.1* | 94947714 | G > C | — | -/TOL | Decreased (Wang et al., 2008; Gu et al., 2010) | Intron | I3 | ||
| rs9332232 | rs9332232 | 13.60 | 11.95 | 11 | 0.2* | 94986275 | T > C | — | -/TOL | — | Intron | I8 | ||
| rs9332241 | rs9332241 | 7.02 | 3.78 | 5 | 0* | 94989116 | C > T | — | -/TOL | — | 3′ UTR | E9 | ||
| CYP2C19 | rs4244285 | CYP2C19*2 | 16.23 | 17.02 | 15 | 14.51 | 94781859 | G > A | Pro218 | -/TOL | Decreased (Dandara et al., 2001) | Synonymous | E5 | |
| rs12248560 | CYP2C19*17 | 15.79 | 23.52 | — | 22.37 | 94761900 | C > T | — | -/DEL | Increased (Sim et al., 2006; Gawrońska-Szklarz et al., 2012) | Upstream Gene | - | ||
| rs7902257 | CYP2C19*27 | 13.60 | 8.25 | — | 0.1* | 94761665 | G > A | — | -/- | Uncertain (Helsby and Burns, 2012) | Upstream Gene | - | ||
| NOVEL_94779010 | Novel-11 | 6.58 | — | — | — | 94779010 | G > A | — | -/TOL | — | Intron | I3 | ||
| rs17879992 | rs17879992 | 11.84 | 9.76 | — | 6.96 | 94775871 | T > C | — | -/TOL | — | Intron | I3 | ||
| rs17884938 | rs17884938 | 9.21 | 5.82 | — | 0.2* | 94780934 | T > A | — | -/TOL | — | Intron | I4 | ||
| rs17885567 | rs17885567 | 5.70 | 5.60 | 10 | 0* | 94850227 | C > T | — | -/TOL | — | Intron | I8 | ||
| rs4917623 | rs4917623 | 10.96 | 19.82 | 22** | 50.8** | 94849811 | T > C | — | -/TOL | — | Intron | I7 | ||
| rs4986894 | rs4986894 | 14.91 | 16.26 | 15 | 14.51 | 94762608 | T > C | — | -/DEL | — | Upstream Gene | - | ||
| rs76267522 | rs76267522 | 5.26 | 2.34 | — | 0.1* | 94780959 | T > C | — | -/TOL | — | Intron | I4 | ||
| −1 | CYP2D6 | rs28371706 | CYP2D6*17 | 16.67 | 21.80 | 20 | 0.2* | 42129770 | G > A | Thr107Ile | TOL/- | Decreased (Masimirembwa et al., 1996) | Missense | E2 |
| rs17002853 | rs17002853 | 5.70 | 0* | — | 0.1* | 42128325 | A > G | Leu231Pro | DEL/- | — | Missense | E5 | ||
| rs28371702 | rs28371702 | 75.88 | 77.08 | 29* | 54.77* | 42129950 | A > C | — | -/- | Normal/Decreased (Zhang et al., 2021) | Intron | I1 | ||
| CYP3A4 | NOVEL_99761942 | Novel-12 | 7.89 | — | — | — | 99761942 | T > C | — | -/TOL | — | Intron | I11 | |
| NOVEL_99764101 | Novel-13 | 7.89 | — | — | — | 99764101 | T > C | — | -/TOL | — | Intron | I9 | ||
| NOVEL_99766252 | Novel-14 | 5.26 | — | — | — | 99766252 | C > T | — | -/TOL | — | Intron | I10 | ||
| NOVEL_99764034 | Novel-15 | 16.23 | — | — | — | 99764034 | C > T | — | -/TOL | — | Intron | I11 | ||
| NOVEL_99764099 | Novel-16 | 8.33 | — | — | — | 99764099 | C > T | — | -/TOL | — | Intron | I12 | ||
| NOVEL_99762108 | Novel-17 | 16.23 | — | — | — | 99762108 | T > C | Ile396Val | TOL/DEL | — | Missense | E11 | ||
| NOVEL_99762115 | Novel-18 | 7.46 | — | — | — | 99762115 | C > T | Val393 | -/TOL | — | Synonymous | E11 | ||
| NOVEL_99762116 | Novel-19 | 7.46 | — | — | — | 99762116 | A > G | Val393Ala | TOL/DEL | — | Missense | E11 | ||
| NOVEL_99784449 | Novel-20 | 15.35 | — | — | — | 99784449 | A > G | — | -/DEL | — | Upstream Gene | — | ||
| NOVEL_99784471 | Novel-21 | 11.40 | — | — | — | 99784471 | T > A | — | -/DEL | — | Upstream Gene | — | ||
| rs1006181087 | rs1006181087 | 8.33 | 0* | — | — | 99762118 | C > T | Val392 | -/TOL | — | Synonymous | E11 | ||
| rs12721622 | rs12721622 | 9.65 | 4.39 | — | 0* | 99768236 | A > T | — | -/TOL | — | Intron | I7 | ||
| rs1479820461 | rs1479820461 | 99.12 | 0* | — | 0* | 99783699 | G > C | — | -/DEL | — | ntron | I1 | ||
| rs2687110 | rs2687110 | 62.28 | 59.23 | — | 99.7** | 99773128 | A > T | — | -/TOL | - | Intron | I3 | ||
| rs2687116 | rs2687116 | 23.25 | 27.91 | — | 97.02** | 99768320 | C > A | — | -/TOL | Decreased (Panczyk, 2014) | Intron | I7 | ||
| rs28988583 | rs28988583 | 11.84 | 8.70 | — | 2.09* | 99769086 | A > G | — | -/TOL | — | Intron | I6 | ||
| rs3735451 | rs3735451 | 82.02 | 81.39 | — | 9.94* | 99758352 | T > C | — | -/TOL | — | Intron | I13 | ||
| rs746971934 | rs746971934 | 8.33 | 0* | — | — | 99762120 | C > A | Val392Leu | DEL/DEL | — | Missense | E11 | ||
| rs778270963 | rs778270963 | 15.79 | 0* | — | — | 99762101 | C > A | Ser398Ile | TOL/- | — | Missense | E11 | ||
| rs915268104 | rs915268104 | 6.58 | 0* | — | — | 99783718 | C > T | — | -/DEL | — | Intron | I1 | ||
| CYP3A5 | rs776746 | CYP3A5*3 | 15.79 | 18 | 77.6** | 94.33** | 99672916 | T > C | — | -/- | Inactive (Kuehl et al., 2001; Sanghavi et al., 2017) | Intron | I3 | |
| rs10264272 | CYP3A5*6 | 15.35 | 15.43 | 22 | 0.3* | 99665212 | C > T | Lys208 | -/DEL | Inactive (Kuehl et al., 2001; Sanghavi et al., 2017) | Synonymous | E7 | ||
| NOVEL_99672254 | Novel-22 | 15.79 | — | — | — | 99672254 | G > A | — | -/TOL | — | Intron | I4 | ||
| NOVEL_99672211 | Novel-23 | 97.81 | — | — | — | 99672211 | G > C | — | -/TOL | — | Intron | I4 | ||
| NOVEL_99672251 | Novel-24 | 5.26 | — | — | — | 99672251 | C > T | — | -/TOL | — | Intron | I4 | ||
| NOVEL_99672285 | Novel-25 | 15.35 | — | — | — | 99672285 | C > T | — | -/TOL | — | Intron | I4 | ||
| NOVEL_99666556 | Novel-26 | 6.14 | — | — | — | 99666556 | A > G | — | -/DEL | — | Intron | I6 | ||
| rs1039108105 | rs1039108105 | 9.21 | 0* | — | 0* | 99656082 | G > C | — | -/TOL | — | Intron | I10 | ||
| rs1458424958 | rs1458424958 | 5.26 | 0* | — | 0* | 99673203 | A > G | — | -/TOL | — | Intron | I3 | ||
| rs1462057054 | rs1462057054 | 16.67 | 0* | — | 0* | 99672249 | A > G | — | -/TOL | — | Intron | I4 | ||
| rs2040992 | rs2040992 | 100 | 99.92 | — | 98.61 | 99664949 | G > A | — | -/DEL | — | Intron | I7 | ||
| rs41303322 | rs41303322 | 10.53 | 11.88 | — | 0* | 99664999 | T > C | — | -/TOL | — | Intron | I7 | ||
| rs4646453 | rs4646453 | 9.21 | 8.77 | — | 1.89* | 99662739 | C > A | — | -/TOL | — | Intron | I13 | ||
| rs6976017 | rs6976017 | 20.18 | 13.99 | — | 3.08* | 99652376 | G > A | — | -/TOL | — | Intron | I11 | ||
| rs8175345 | rs8175345 | 9.65 | 8.09 | — | 0* | 99672695 | G > A | — | -/DEL | — | Intron | I3 | ||
* and ** represents a significantly higher or lower difference in the minor allele frequency (MAF) in this Zimbabwean (ZIM) study population compared to the reported MAF in the African (AFR)/European (EUR) population in the 1,000 Genomes Project using Pearson’s chi-square tests.
SIFT, sorting Intolerant From Tolerant; GWAVA, Genome-Wide Annotation of Variants; DEL, Deleterious effect on protein function; TOL, Tolerated effect on protein function. Region described by: Exon (E) and Intron (I). CYP, Cytochrome P450 enzyme.