The genetic variants identified in cynomolgus CYP2C76
Variant | Exon | Nucleotide Changea | Amino Acid Change | Location on cDNA | Allele Frequency | Site | Kinetic Parametersb | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Indochina (n = 78) | Indonesia (n = 68) | Km | Vmax | ||||||||
| c.178G>T | 2 | caaaa(G>T)attat | D60Y | 178 | 0.513 | 0.500 | N.D. | N.D. | |||
| c.193C>T | 2 | ctgtg(C>T)tcact | L65F | 193 | 0.513 | 0.500 | N.D. | N.D. | |||
| c.241G>A | 2 | gatac(G>A)aagca | E81K | 241 | 0.513 | 0.500 | N.D. | N.D. | |||
| c.449TG>A | 3 | agcct(TG>A)tgtct | Frameshift | 449 | 0 | 0.020d | N.D. | N.D. | |||
| c.707A>T | 5 | aaatt(A>T)tgctc | Y236F | 707 | 0.936 | 1.000 | SRS3 | 710 | 412 | ||
| c.883A>G | 6 | tgttt(A>G)gtgca | S295G | 883 | 0.013 | 0 | SRS4 | 824 | 927 | ||
| c.928A>T | 6 | gactg(A>T)tgctc | M310L | 928 | 0.731 | 1.000 | N.D. | N.D. | |||
| c.968G>A | 7 | agtgc(G>A)ggaag | R323Q | 968 | 0.231 | 0 | N.D. | N.D. | |||
| c.1292A>Gc | 9 | aggaa(A>G)aagaa | K431R | 1292 | 0 | 0 | Heme binding | 836 | 1393 | ||
| c.1436C>T | 9 | tatac(C>T)accct | P479L | 1436 | 0.205 | 0.074 |
| N.D. | N.D. | ||
N.D., not determined.
↵ a Nucleotide changes were detected by comparing with the CYP2C76 cDNA sequence (GenBank accession no. DQ074807) as a reference sequence.
↵ b Km (μM) and Vmax (pmol/min/nmol CYP) of each recombinant protein was determined with tolbutamide methyl-hydroxylation, for which the detection limit was 40 pmol/ml. The Km and Vmax for the CYP2C76 of the reference sequence were 704 and 1570, respectively.
↵ c This allele was identified by searching the EST database and was not found in any genome samples that were analyzed in this study.
↵ d For c.449TG>A, 204 animals in the Indonesian population were used to calculate allele frequency.