Reports
Clinical Pharmacology & Therapeutics advance online publication 11 June 2008. doi:10.1038/clpt.2008.103
The Consequence of Concomitantly Present Functional Genetic Variants for the Identification of Functional Genotype–Phenotype Associations in Pain
J Lötsch1, K Flühr1, T Neddermayer1, A Doehring1 and G Geisslinger1
1pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Frankfurt am Main, Frankfurt, Germany
Correspondence: J Lötsch, (j.loetsch@em.uni-frankfurt.de)
Received 16 January 2008; Accepted 1 April 2008; Published online 11 June 2008.
Abstract
Genetics-based personalized approaches to pain management have received a setback because of the nonreproducibility of functional genetic associations such as the pain-modulatory effect1,2 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.
