Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2754_Библиотеки_им_академика_М_И_Перельмана

While some organizations, such as the National Academy of Clinical Biochemistry (NACB), have established practice guide linesfor the application of pharmacogenetics, clinical guidance forpharmacogenetic tests is oen provided in disease-specic guidelines on a case-by-case basis. Administration (FDA) has released both a Table of Pharma­cogenetic Associations (https://www.fda.gov/medical-devices

e CYP2D6 gene contains more than 120 alleles, which can lead to a normal function, reduced function, or no function. Increased CYP2D6 function is also observed when there are multiple copies of the gene present. e most common no­function alleles are *3 (rs35742686), *4 (rs1065852, rs3892097, and rs1135840), *5 (gene deletion), and *6 (rs5030655). ese single nucleotide polymorphism (SNP) reference numbers (rs numbers) are curated reference numbers for specic variants established by the National Center for Biotechnology Informa­tion (NCBI) SNP database (Database of Single Nucleotide Poly­morphisms [dbSNP] at www.ncbi.nlm.nih.gov/snp). Multiple copies of the gene are designated by the allele number, the letterx, the the number of copies detected (e.g., *1x2). Due to thenumber of CYP2D6 alleles and their disparate functional consequences, the conversion of diplotypes to standardized and clinically interpretable metabolizer phenotypes becomes particularly important. devised in which a numeric value is given to each allele, scores are summed for both alleles, and the resulting numeric value is converted into a CYP2D6 metabolizer phenotype. Each functional group is assigned an activity value ranging from 0to 1 (eg,0 for no function, 0.5 for decreased function, and 1 for normal function). If multiple copies of the CYP2D6 gene are detected, the activity score is multiplied by the number of copies of each allele present. erefore, a normal metabolizer with an activity score of 1.5 will have less enzymatic activity than a normal metabolizer with an activity score of 2. CYP2D6 metabolizer phenotypes include CYP2D6 ultrarapid metabo lizer (activity score >2.25), normal metabolizer (activity score is 1.25 to 2.25), intermediate metabolizer (activity score is 0.25 to 1), and poor metabolizer (activity score is 0). CYP2D6 poor metabolizers are more common among individuals of European ancestry and CYP2D6 ultrarapid metabolizers are more common in individuals with Oceania and Near East ancestry.