Copy number variants in pharmacogenetic genes

Abstract

Variation in drug efficacy and toxicity remains an important clinical concern. Presently, single nucleotide polymorphisms (SNP) only explain a portion of this problem, even in situations where the pharmacological trait is clearly heritable. The Human CNV Project identified copy number variations (CNVs) across approximately 12% of the human genome, and these CNVs were considered causes of diseases. Although the contribution of CNVs to the pathogenesis of many common diseases is questionable, CNVs play a clear role in drug related genes by altering drug metabolizing and drug response. Here we provide a comprehensive review of the clinical relevance of CNVs to drug efficacy, toxicity, disease prevalence in world populations and discuss the implication of using CNVs as diagnosis in clinical intervention.

High-resolution melting analysis of 15 genes in 60 patients with cytochrome-c oxidase deficiency

“…Thus, it is evident that every human individual is a complex variable mosaic of potential pathogenic variants, which is in accordance with the results from exome sequencing and whole-genome microarray analyses. [50][51][52] Nevertheless, an additional study of the four non-synonymous variations, p.R85W (COX4I2), p.R71H (COX5A), p.K31del (COX7A1) and p.R431W (COX10), should be performed to evaluate their pathogenicity, significance and severity. Cells with stable downregulated expression of individual subunits may be utilized.…”

TBHEB 2014-1 Vol 71 Full Printed Journal

“…In some studies, imipenem and meropenem were the most effective agent against the nonfermenters (16,18,20). In a different study, resistance percentage of meropenem and imipenem were 16-54.3% for A. baumannii strains and 15-29% for P. aeruginosa strains (17,19).…”

“…Kaynar ve ark. 'nın yaptığı diğer bir çalışmada; tıbbi gözetim altında kullanılan enteral beslenme ürünlerindeki vitamin B 6 miktarlarını mikrobiyolojik yöntem ile 0,13 -0,65 mg/100 mL arasında tespit etmişlerdir (18). Tespit edilen değerlerin etikette yer alan değerlere uygunluğu görülmüştür.…”

Genomic structural variation in affective, anxiety, and stress-related disorders

“…Interindividual pharmacokinetic variability has been shown to be substantially driven by variation in genes coding for cytochrome P450 (CYP) enzymes, which determine the hepatic metabolic rate of a variety of drugs (see Kirchheiner et al 2004). In addition to single nucleotide polymorphisms (SNPs), CNVs have been shown to influence CYP gene activity and thus drug efficacy and toxicity (He et al 2011;Martis et al 2013). On a pharmacodynamic level, Rasmussen and Dahmcke (2012) investigating the impact of genetic variation on response to 876 drugs in a genome-wide approach identified 1,721 structural variants affecting drug target encoding genes.…”