Copy number variation and gene rearrangements in CYP2D6 genotyping using multiplex ligation-dependent probe amplification in Koreans

AIM: The present study introduces a simple method for CYP2D6 genotyping that not only determines the heterozygous or homozygous deletions and duplications, but also distinguishes tandem hybrids. MATERIALS & METHODS: Using two commercially available methods, 49 Korean male subjects were genotyped for CYP2D6. The Affymetrix(®) Targeted Human Drug Metabolizing Enzymes and Transporter 1.0 Assay was used for SNP genotyping and multiplex ligation-dependent probe amplification (MLPA) assay (SALSA(®) MLPA(®) Kit P128-A1 CYP450) was used for copy number analysis. Long range PCR was used to confirm the MLPA results. Fifty Caucasian samples obtained from the Coriell Institute were used to confirm the accuracy of the MLPA assay. RESULTS: Using two commercially available methods, we found seven different allele types with CYP2D6*1 (34.7%), *2 (12.2%), *10 (17.4%) and *36-*10 (22.5%) being the most common alleles in the Korean population. The MLPA results showed 100% agreement with long-range-PCR results and were able to distinguish deletions and duplications among 50 Caucasian reference samples. CONCLUSION: The application of MLPA-based genotyping to routine clinical analysis will enable patients to be assigned to more accurate genotypes at a reasonable cost in a large number of individuals at the majority of locations.ope