The consequence of concomitantly present functional genetic variants for the identification of functional genotype-phenotype associations in pain.
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 of the catechol-O-methyl transferase (COMT) gene 472G>A single-nucleotide polymorphism. 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.
Pharmazentrum frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Frankfurt am Main, Frankfurt, Germany. j.loetsch@em.uni-frankfurt.de
J
J
Lötsch
K
K
Flühr
T
T
Neddermayer
A
A
Doehring
G
G
Geisslinger
D000293:Adolescent; D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000235:genetics*; D017288:Pain Threshold; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
D002394:Catechol O-Methyltransferase