CYP3A5 Genotype

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PackagingCharacterization ProvidedSafety, Handling, and Storage

 

They are prepared from individual donors characterized for three CYP3A5 allelic categories, high activity (*1/*1), moderate activity (*1/*3) and no activity (*3/*3). Microsomes are available from each CYP3A5 genotype category.

Members of the CYP3A family are the most abundant CYP enzymes in the human liver and intestine, influencing circulating steroid levels and responsible for the oxidative metabolism of half of all drugs. When it is present, CYP3A5 can represent up to 50% of the total CYP3A protein in liver microsomes, suggesting an important role in the clearance of CYP3A substrates.

Base change 6986A>G constitutes the molecular basis of splicing defect present in CYP3A5*3 allele. The allele is associated with decreased in vivo or severely decreased in vitro enzymatic activity (www.cypalleles.ki.se). HLM microsomes from CYP3A5*3/*3 donors are offered in the no-activity category. Other alleles of reduced or no activity, such as CYP3A5*6 and CYP3A5*7, were identified in Africans (Roy, et al., 2005).

There are substantial CYP3A expression differences between individuals, which contributes greatly to variation in oral bioavailability and systemic clearance of CYP3A substrates. There are also pronounced inter-racial differences in CYP3A5 allelic frequency. The table below demonstrates allelic frequency variations among different races.

CYP3A5 Allele Frequency

Allele	African American	Asian	Caucasian	Hispanic
CYP3A5*1	0.45 – 0.73	0.15 – 0.38	0.05 – 0.15	0.25
CYP3A5*3	0.06 – 0.50	0.60 – 0.76	0.82 – 0.96	0.46 – 0.71

Adapted from Thompson, et al. 2004, Wang, et al. 2006, Kuehl, et al. 2001 and Lamba, et al. 2002.

Human livers are characterized by genotype in a combined approach with both PCR and Western blot techniques to distinguish between three CYP3A5 allelic categories.

Packaging

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

Characterization Provided

• Genotype of CYP3A5
• 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 6β-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
H3A5.HA	CYP3A5 High Activity (*1/*1)	0.5 mL at 20 mg/mL
H3A5.MA	CYP3A5 Moderate Activity (*1/*3)	0.5 mL at 20 mg/mL
H3A5.NA	CYP3A5 No Activity (*3/*3)	0.5 mL at 20 mg/mL