CYP2D6 Genotype

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PackagingCharacterization ProvidedSafety, Handling, and Storage

 

On the high end of the CYP2D6 activity spectrum, we offer microsomes from donors carrying duplication of fully active alleles, referred to as ultra rapid metabolizers. On the low end of the CYP2D6 activity spectrum, we provide microsomes from donors carrying two inactive alleles.

CYP2D6 expressed more alleles than  any other drug-metabolizing human P450 enzyme. Genetic polymorphism is the most common cause of the interindividual differences in metabolism of CYP2D6 substrates. Detailed descriptions of the nucleotide changes characterizing individual alleles and their effects on the CYP2D6 phenotype can be found at www.cypalleles.ki.se.

Liver donor DNA was analyzed with the restriction fragment length polymorphism (RFLP) protocol, (Gaedigk, A., Bradford, L.D., Marcucci, K.A. and Leeder, J.S. Unique CYP2D6 activity distribution and genotype–phenotype discordance in African Americans. Clin. Pharmacol. Ther. 72, 76–89 (2002)) with later modifications.

Genotypes present in our collection are organized based on activity score as defined by Gaedigk, et. al, 2008. This is a numerical expression based on the presence of fully-, partially-functional and non-functional alleles, shown here in Table 1.

Table 1. Values assigned to CYP2D6 alleles in the Activity Score

Value assigned to allele	Alleles
2	Gene duplication of fully-functional allele e.g., *2x2
1	Fully-functional allele e.g., *1, *2
0.5	Partially-functionsal alleles e.g., *9, *17, *29, *41
0	Non-functional alleles e.g., *3, *4, *5, *6

Adapted from A Gaedigk, SD Simon, RE Pearce, LD Bradford, MJ Kennedy and JS Leeder. The CYP2D6 Activity Score: Translating Genotype Information into a Qualitative Measure of Phenotype. Clin Pharmacol Ther. 83(2), 234-42 (2008)

Table 2. CYP2D6 Activity Score and the corresponding donor genotypes in the XenoTech collection of individual human liver microsomes

Activity Score	Genotype	Product Category
3	*1/*2x2	High Activity (H2D6.HA)
2.5	*2x2/*41	Moderate Activity (H2D6.MA)
2	*1/*1, *1/*2, *2/*2	Moderate Activity (H2D6.MA)
1.5	*1/*9, *1/*29, *1/*41, *2/*41	Moderate Activity (H2D6.MA)
1	*1/*3, *1/*4, *1/*5, *2/*3, *2/*4, *17/*29, *41/*41	Moderate Activity (H2D6.MA)
0.5	*4/*9, *4/*41, *5/*41, *6/*9	Moderate Activity (H2D6.MA)
0	*4/*4, *4/*5, *4/*6	No Activity (H2D6.NA)

Multiple donors are available for most genotype categories

Packaging

Concentration: 20 mg/mL
Suspension buffer: 250 mM sucrose

Characterization Provided

• Genotype for CYP2D6
• Specific content of cytochrome P450
• Specific content of cytochrome b5
• NADPH-cytochrome c reductase activity
• CYP1A2 Phenacetin O-dealkylation
• CYP2A6 Coumarin 7-hydroxylation
• CYP2B6 Bupropion hydroxylation
• CYP2C8 Amodiaquine N-dealkylation
• CYP2C9 Diclofenac 4´-hydroxylation
• CYP2C19 S-Mephenytoin 4´-hydroxylation
• CYP2D6 Dextromethorphan O-demethylation
• CYP2E1 Chlorzoxazone 6-hydroxylation
• CYP3A4/5 Testosterone 6ß-hydroxylation
• CYP3A4/5 Midazolam 1´-hydroxylation
• CYP4A11 Lauric acid 12-hydroxylation
• Donor information (age, ethnicity, gender, cause of death and infectious disease status)

Safety, Handling, and Storage

Informed Consent Statement

A single organization regulates and oversees the use of human tissue intended for transplantation in the United States, namely the United Network for Organ Sharing (UNOS). Organ donors may elect to have their organs used either for transplantation only, or for transplantation or research. Thus, the donor (or the donor's family) has the right to prevent the use of the donor's organs for research. Regardless of the use of donated organs, no compensation is given to the donor’s family; any such compensation is illegal in the United States. In those cases where donors (or family members) elect to withhold organs from research uses, any organs that cannot be transplanted are discarded.

XenoTech receives hepatic, renal, intestinal, pulmonary, and other human tissue from various regional organ procurement organizations (OPOs) that obtain organs approved for research use. Regulations in the United States require that, regardless whether the organ is intended for transplantation or research purposes, the organ donor's identity be treated as highly confidential information. Organ procurement organizations maintain the informed consent records from each donor, and our Standard Operating Procedure requires that XenoTech personnel confirm the existence of informed consent for research purposes, prior to transport of organs to XenoTech. This procedure is intended to ensure that XenoTech manufactures human-derived products only when informed consent has been granted for research use of those specific organs. XenoTech does not, and, in consideration of confidentiality, cannot obtain the informed consent records from these organizations.

All human tissue accepted by XenoTech has been tested for the possible presence of various infectious diseases, and XenoTech does not accept human-derived material unless the donor has tested negative (non-reactive) for RPR, HIVAb, HTLVAb, HBsAg and HCVAb. All human tissue is also tested for CMVAb.  However, due to the widespread (nearly ubiquitous) appearance of CMV in the population, and its relative insignificance as an infectious agent, tissues from donors reactive for CMVAb are accepted.  The serology status of each donor is typically determined by ELISA by the organ procurement hospital.

XenoTech does not deal directly with - nor does it make any direct payments to - the surgeons who procure organs or the medical institutions where they work.

Caution

In the case of human tissue, XenoTech accepts only non-transplantable tissue from donors who test negative for HIV 1 and 2, HTLV, and Hepatitis B and C. However, as a precaution, all human-de­rived samples should be regarded as a potential bio­hazard and should be stored, handled and discarded accordingly. Cellular and subcellular fractions are intended for in vitro use only.

Products

Product #	Name	Amount
H2D6.HA	CYP2D6 High Activity (Activity score = 3)	0.5 mL at 20 mg/mL
H2D6.MA	CYP2D6 Moderate Activity (Activity score = 0.5-2.5)	0.5 mL at 20 mg/mL
H2D6.NA	CYP2D6 No Activity (Activity score = 0)	0.5 mL at 20 mg/mL