Allelic distributions of CYP2D6 gene copy number variation in the Eastern Han Chinese population
Abstract
Aim: The human cytochrome P450 2D6 (CYP2D6) gene copy number variation,
involving CYP2D6 gene deletion (CYP2D6*5) and duplication or multiduplication
(CYP2D6*×N), can result in reduced or increased metabolism of many clinically
used drugs. The identification of CYP2D6*5 and CYP2D6*×N and the investigation
of their allelic distributions in ethnic populations can be important in determining
the right drug and dosage for each patient. Methods: The CYP2D6*5 and
CYP2D6 genes, and CYP2D6 gene duplication were identified by 2 modified long
PCR, respectively. To determine duplicated alleles, a novel long PCR was developed
to amplify the entire duplicated CYP2D6 gene which was used as template
for subsequent PCR amplification. A total of 363 unrelated Eastern Han Chinese
individuals were analyzed for CYP2D6 gene copy number variation. Results: The
frequency of CYP2D6*5 and CYP2D6*×N were 4.82% (n=35) and 0.69% (n=5) in
the Eastern Han Chinese population, respectively. Of the 5 duplicated alleles, 3
were CYP2D6*1×N and 2 were CYP2D6*10×N. One individual was a carrier of
both CYP2D6*5 and CYP2D6*1×N. Taken together, the CYP2D6 gene rearrangements
were present in 10.74% of subjects. Conclusion: Allelic distributions
of the CYP2D6 gene copy number variation differ among Chinese from different
regions, indicating ethnic variety in Chinese. Long PCR are convenient, cost
effective, specific and semiquantitative for the detection of the CYP2D6 gene
copy number variation, and amplification of the entire duplicated CYP2D6 gene is
necessary for the accurate identification of duplicated alleles.
Keywords:
involving CYP2D6 gene deletion (CYP2D6*5) and duplication or multiduplication
(CYP2D6*×N), can result in reduced or increased metabolism of many clinically
used drugs. The identification of CYP2D6*5 and CYP2D6*×N and the investigation
of their allelic distributions in ethnic populations can be important in determining
the right drug and dosage for each patient. Methods: The CYP2D6*5 and
CYP2D6 genes, and CYP2D6 gene duplication were identified by 2 modified long
PCR, respectively. To determine duplicated alleles, a novel long PCR was developed
to amplify the entire duplicated CYP2D6 gene which was used as template
for subsequent PCR amplification. A total of 363 unrelated Eastern Han Chinese
individuals were analyzed for CYP2D6 gene copy number variation. Results: The
frequency of CYP2D6*5 and CYP2D6*×N were 4.82% (n=35) and 0.69% (n=5) in
the Eastern Han Chinese population, respectively. Of the 5 duplicated alleles, 3
were CYP2D6*1×N and 2 were CYP2D6*10×N. One individual was a carrier of
both CYP2D6*5 and CYP2D6*1×N. Taken together, the CYP2D6 gene rearrangements
were present in 10.74% of subjects. Conclusion: Allelic distributions
of the CYP2D6 gene copy number variation differ among Chinese from different
regions, indicating ethnic variety in Chinese. Long PCR are convenient, cost
effective, specific and semiquantitative for the detection of the CYP2D6 gene
copy number variation, and amplification of the entire duplicated CYP2D6 gene is
necessary for the accurate identification of duplicated alleles.