Variant:

rs28371706 at chr22:42525772 in CYP2D6 (VIP)

Variant Annotations

PharmGKB variant annotations provide information about variant-drug pairs based on individual PubMed publications. Each annotation represents information from a single paper and the goal is to report the information that the author states, not an interpretation of the paper. The PMID for supporting PubMed publications is found in the "Evidence" field.

Information presented, including study size, allele frequencies and statistics is taken directly from the publication. However, if the author does not correct p-values in cases of multiple hypotheses, curators may apply a Bonferroni correction. Curators attempt to report study size based on the actual number of participants used for the calculation of the association statistics, so the number may vary slightly from what is reported in the abstract of the paper. OMB Race Category information is derived from the paper and mapped to standardized categories. Category definitions may be found by clicking on the "OMB Race Category" link.

There are 2 annotations for this variant. Register or sign in to see them.

VIP Variant in CYP2D6

CYP2D6 1023C>T (also seen as 1111C>T in the literature) was first identified when screening for reduced function alleles in a Zimbabwean population [Article:8971426]. It was identified as being part of the reduced function haplotype CYP2D6*17. According to the genotyping algorithm of Gaedigk et al [Article:1063413], the presence of CYP2D6 1023C>T (1111C>T) and 2850C>T (2938C>T) is diagnostic for CYP2D6*17.
A subsequent study examined the role of CYP2D6 1023C>T and two other SNPs found in CYP2D6*17 to see which of the SNPs was causative of the reduced function observed with the haplotype [Article:9415713]. The authors found that the CYP2D6 1023C>T single mutation exhibited normal function in transfected COS-1 cells, but when made in combination with another mutation led to an increased Km (decreased affinity) for bufuralol. Interestingly, when the substrate was codeine, CYP2D6 1023C>T alone was sufficient to cause an increase in the Km of CYP2D6 for codeine, suggesting that this mutation exhibits substrate-specific effects, and may contribute to the reduction in function of CYP2D6*17.

Note: The CYP2D6 gene is found on the minus chromosomal strand. Please note that for standardization, the PharmGKB presents all allele base pairs on the positive chromosomal strand, therefore the alleles within our variant annotations will differ (in a complementary manner) from those in this VIP summary that are given on the minus strand as reported in the literature.

Publications related to rs28371706 at chr22:42525772: 5

VA	Exploration of CYP450 and drug transporter genotypes and correlations with nevirapine exposure in Malawians. Pharmacogenomics. 2012. Brown Kevin C, et al. [Article:22111602@PubMed]
VA	The pharmacokinetics of codeine and its metabolites in Blacks with sickle cell disease. European journal of clinical pharmacology. 2009. Shord Stacy S, et al. [Article:19357842@PubMed]
VIP	Optimization of cytochrome P4502D6 (CYP2D6) phenotype assignment using a genotyping algorithm based on allele frequency data. Pharmacogenetics. 1999. Gaedigk A, et al. [Article:10634130@PubMed]
VIP	A combination of mutations in the CYP2D6*17 (CYP2D6Z) allele causes alterations in enzyme function. Molecular pharmacology. 1997. Oscarson M, et al. [Article:9415713@PubMed]
VIP	A novel mutant variant of the CYP2D6 gene (CYP2D6*17) common in a black African population: association with diminished debrisoquine hydroxylase activity. British journal of clinical pharmacology. 1996. Masimirembwa C, et al. [Article:8971426@PubMed]

Cross-References

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