CNVs of human genes and their implication in pharmacogenetics

Johansson, Inger; Ingelman‐Sundberg, Magnus

doi:10.1159/000184709

Cited by 31 publications

(25 citation statements)

References 173 publications

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“…When we used this approach to genotype DNA samples from 761 randomly selected Caucasian women for the three common SULT1A1 functional SNPs (two in the gene promoter and the SULT1A1 * 2 non-synonymous SNP), we observed every possible combination of SNP genotypes for the duplicated alleles ( Table 2 ). This observation contrasts with the situation for the functionally and clinically relevant cytochrome P450 gene CYP2D6, a gene that has also undergone deletion and duplication in the course of evolution (Johansson et al, 1993;Dalen et al, 1998;Johansson and Ingelman-Sundberg, 2008). When multiple copies of CY-P2D6 are present, they generally involve only a single duplicated allele, not the variety of combinations that we observed for SULT1A1 ( Table 2 ).…”

Section: Sult1a1 Cnvscontrasting

confidence: 84%

“…The initial focus of pharmacogenetics has understandably been on SNPs. However, the examples provided by SULT1A1 and CYP2D6 (Johansson and Ingelman-Sundberg, 2008) make it clear that both SNPs and CNVs may need to be taken into account to successfully link genotypic variation to variation in drug response phenotypes. Once techniques are developed that make this process efficient, accurate, and cost effective, there can be little doubt that both the 'discovery phase' of pharmacogenetics and pharmacogenetic clinical assays will -when appropriate -routinely obtain both CNV data and SNP genotyping, as described here for SULT1A1, to help make it possible to better individualize drug therapy.…”

Section: Resultsmentioning

confidence: 99%

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Sulfotransferase gene copy number variation: pharmacogenetics and function

Hebbring

Moyer

Weinshilboum³

2008

Cytogenet Genome Res

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Pharmacogenetics is the study of the role of inheritance in variation to drug response. Drug response phenotypes can vary from adverse drug reactions at one end of the spectrum to equally serious lack of the desired effect of drug therapy at the other. Many of the current important examples of pharmacogenetics involve inherited variation in drug metabolism. Sulfate conjugation catalyzed by cytosolic sulfotransferase (SULT) enzymes, particularly SULT1A1, is a major pathway for drug metabolism in humans. Pharmacogenetic studies of SULT1A1 began over a quarter of a century ago and have advanced from biochemical genetic experiments to include cDNA and gene cloning, gene resequencing, and functional studies of the effects of single nucleotide polymorphisms (SNPs). SNP genotyping, in turn, led to the discovery of functionally important copy number variations (CNVs) in the SULT1A1 gene. This review will briefly describe the evolution of our understanding of SULT1A1 pharmacogenetics and CNV, as well as challenges involved in utilizing both SNP and CNV data in an attempt to predict SULT1A1 function. SULT1A1 represents one example of the potential importance of CNV for the evolving disciplines of pharmacogenetics and pharmacogenomics.

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Section: Sult1a1 Cnvscontrasting

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Sulfotransferase gene copy number variation: pharmacogenetics and function

Hebbring

Moyer

Weinshilboum³

2008

Cytogenet Genome Res

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“…Many groups have addressed the presence of CNV in the human genome and their associations with common human diseases including neuropsychiatric, autoimmune, infectious and cardiovascular diseases[15, 16], while others found evidence that CNVs are not associated with common diseases [17]. While the contribution of CNVs to the pathogenesis of common diseases is questionable, CNVs in some pharmacogenetic genes play a clear role in drug efficacy and toxicity [18]. Inspired by the increasing interest in CNVs, here we review our current knowledge of CNVs in relation to drug efficacy and toxicity, their prevalence in ethnically diverse populations, and the potential utilization of CNV knowledge in the clinical setting.…”

Section: What Is a Copy Number Variant?mentioning

confidence: 99%

Copy number variants in pharmacogenetic genes

Hoskins

McLeod

2011

Trends in Molecular Medicine

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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.

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“…Some of the strongest evidence that this is the case comes from the observation that an increase in amylase gene copy number is associated with an increased enzymatic activity and starch digestion [77]. Some have proposed that copy number may account for about 25% individual variation in response [78]. …”

Section: Nutrigenetics/nutrigenomics In Cancer Control and Managementmentioning

confidence: 99%

Nutrigenetics and Nutrigenomics: Viewpoints on the Current Status and Applications in Nutrition Research and Practice

et al. 2011

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Nutrigenetics and nutrigenomics hold much promise for providing better nutritional advice to the public generally, genetic subgroups and individuals. Because nutrigenetics and nutrigenomics require a deep understanding of nutrition, genetics and biochemistry and ever new ‘omic’ technologies, it is often difficult, even for educated professionals, to appreciate their relevance to the practice of preventive approaches for optimising health, delaying onset of disease and diminishing its severity. This review discusses (i) the basic concepts, technical terms and technology involved in nutrigenetics and nutrigenomics; (ii) how this emerging knowledge can be applied to optimise health, prevent and treat diseases; (iii) how to read, understand and interpret nutrigenetic and nutrigenomic research results, and (iv) how this knowledge may potentially transform nutrition and dietetic practice, and the implications of such a transformation. This is in effect an up-to-date overview of the various aspects of nutrigenetics and nutrigenomics relevant to health practitioners who are seeking a better understanding of this new frontier in nutrition research and its potential application to dietetic practice.

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CNVs of human genes and their implication in pharmacogenetics

Cited by 31 publications

References 173 publications

Sulfotransferase gene copy number variation: pharmacogenetics and function

Sulfotransferase gene copy number variation: pharmacogenetics and function

Copy number variants in pharmacogenetic genes

Nutrigenetics and Nutrigenomics: Viewpoints on the Current Status and Applications in Nutrition Research and Practice

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