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The Consequence of Concomitantly Present Functional Genetic Variants for the Identification of Functional Genotype–Phenotype Associations in Pain
Author(s) -
Lötsch J,
Flühr K,
Neddermayer T,
Doehring A,
Geisslinger G
Publication year - 2009
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2008.103
Subject(s) - single nucleotide polymorphism , genotype , pharmacogenetics , catechol o methyl transferase , genetics , phenotype , confounding , allele , polymorphism (computer science) , genetic variants , biology , gene , medicine
Genetics‐based personalized approaches to pain management have received a setback because of the nonreproducibility of functional genetic associations such as the pain‐modulatory effect 1 , 2 of the catechol‐O‐methyl transferase ( COMT ) gene 472G>A single‐nucleotide polymorphism. 3 , 4 Given that many of the pain‐relevant genetic variants are common (allelic frequencies of 10–50%), we hypothesized that a major reason for difficulties in reproducing demonstrations of genetic influences on pain is the concomitant presence in a single individual of several functional genetic polymorphisms that act as confounders. Clinical Pharmacology & Therapeutics (2008); 85 , 1, 25–30 doi: 10.1038/clpt.2008.103