Genetic variation in the coding regions of the canine CYP2B11 gene - Implications for Veterinary Medicine?

Abstract

In veterinary medicine, the anaesthetic Propofol and the anticancer agent Cyclophosphamide are widely used. These compounds need to be metabolized by a cytochrome and in the canine, CYP2B11 is responsible for this. To further elucidate the cause of variations in metabolism of these compounds, this study aimed to identify and confirm variability in the CYP2B11 gene and predict effects on enzyme phenotype. By PCR reaction, all exonic regions of CYP2B11 in 20 canines of different breeds were amplified and submitted for sequencing. The retrieved sequences were reviewed for variations and these variations were tested to confirm and quantify by Restriction Fragment Length Polymorphism. The sample population consisted of a panel of 100 dogs of 11 breeds and mixed bred dogs, chosen to represent the US dog population. 3 Exonic SNPs were identified; a synonymous G>A SNP in exon 1 (2B11*1) could however not be confirmed and quantified in the larger population. A non-synonymous C>T SNP was found in exon 2 (2B11*2), this was present in the population with an allele frequency of 8% but mainly in Labrador Retrievers. This polymorphism was predicted to have a probable damaging effect on CYP2B11. A potential splice site G>A SNP (2B11*3) was found in exon 7 and showed to be widely distributed, having an allele frequency of 65% in the overall population. Besides these exonic SNPs, two intronic SNPs were identified but not tested to confirm. The reference sequence differed from all tested dogs in exon 6, maybe representing a SNP in the Boxer used for this reference sequence. These polymorphisms could have major effects on the function of CYP2B11 and these results therefore prove a need for further investigation.