Analysis of compound heterozygous CYP2C19 genotypes to determine cis and trans configurations

Pharmacogenomics. 2014 Jun;15(9):1197-205. doi: 10.2217/pgs.14.72.

Abstract

Background: Through allele specific PCR we studied 220 CYP2C19 compound heterozygous samples, of unknown ethnicity, to determine the haplotype for each of the variations within a sample.

Materials & methods: The genotypes assessed were: 180 *2 and *17 samples (100% in trans); 20 *2 and *11 samples (100% in cis); ten *4 and *17 samples (50% of the samples were *1/*4B and 50% *4A/*17); six *2, *11 and *17 samples (100% showed *2 and *11 in cis, and *17 in trans); two *2, *4 and *17 samples (100% *4B with *2 in trans); one sample with *17 and *34 (these were in trans); and one sample that contained *2, *17, c.463G>T (p.E155X; *17 and c.463G>T were in cis, with *2 in trans).

Results & conclusion: In our study, we observed a different frequency for the *4B allele (when a sample contains both *4 and *17); and identified *17 occurring in cis with a novel nonsense allele. Accurately assessing a patient's genotype, including assignment of a haplotype, can be important when making a phenotype prediction.

Keywords: CYP2C19; CYP2C19*11; CYP2C19*17; CYP2C19*2; CYP2C19*4; cis; cytochrome P450 2C19; haplotype; trans.

MeSH terms

  • Alleles
  • Cytochrome P-450 CYP2C19 / chemistry*
  • Cytochrome P-450 CYP2C19 / genetics*
  • Gene Frequency
  • Haplotypes
  • Heterozygote
  • Humans
  • Polymorphism, Single Nucleotide
  • Protein Conformation

Substances

  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19