Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2014 Mar;16(1):83-93.
doi: 10.1007/s12017-013-8255-9. Epub 2013 Aug 21.

Complex Multilocus Effects of catechol-O-methyltransferase Haplotypes Predict Pain and Pain Interference 6 Weeks After Motor Vehicle Collision

Affiliations
Free PMC article
Observational Study

Complex Multilocus Effects of catechol-O-methyltransferase Haplotypes Predict Pain and Pain Interference 6 Weeks After Motor Vehicle Collision

Andrey V Bortsov et al. Neuromolecular Med. .
Free PMC article

Abstract

Catechol-O-methyltransferase, encoded by COMT gene, is the primary enzyme that metabolizes catecholamines. COMT haplotypes have been associated with vulnerability to persistent non-traumatic pain. In this prospective observational study, we investigated the influence of COMT on persistent pain and pain interference with life functions after motor vehicle collision (MVC) in 859 European American adults for whom overall pain (0-10 numeric rating scale) and pain interference (Brief Pain Inventory) were assessed at week 6 after MVC. Ten single nucleotide polymorphisms spanning the COMT gene were successfully genotyped, and nine were present in three haploblocks: block 1 (rs2020917, rs737865, rs1544325), block 2 (rs4633, rs4818, rs4680, rs165774), and block 3 (rs174697, rs165599). After adjustment for multiple comparisons, haplotype TCG from block 1 predicted decreased pain interference (p = 0.004). The pain-protective effect of the low pain sensitivity (CGGG) haplotype from block 2 was only observed if at least one TCG haplotype was present in block 1 (haplotype × haplotype interaction p = 0.002 and <0.0001 for pain and pain interference, respectively). Haplotype AG from block 3 was associated with pain and interference in males only (sex × haplotype interaction p = 0.005 and 0.0005, respectively). These results suggest that genetic variants in the distal promoter are important contributors to the development of persistent pain after MVC, directly and via the interaction with haplotypes in the coding region of the gene.

Conflict of interest statement

CONFLICT OF INTEREST

Dr. Diatchenko is a co-founder and equity stock holder in Algynomics, Inc. Other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) COMT haploblocks and linkage disequilibrium; color and numbers represent D′ values (dark red=high inter-SNP D′; blue=statistically ambiguous high D′; white= statistically ambiguous low inter-SNP D′). (B) COMT haplotypes and haplotype frequencies; thin lines denote haplotype combinations with frequency >1%, thick lines with frequency > 10%.
Figure 2
Figure 2
Haplotype A3 x LPS interactions on overall pain (A) and pain interference (B) at week 6 after motor vehicle collision; plotted values are means ± standard errors of mean; p-values are from the additive genetic model.
Figure 3
Figure 3
Haplotype B2 x sex interactions on overall pain (A) and pain interference (B) at week 6 after motor vehicle collision. Plotted values are means ± standard errors of mean.
Figure 4
Figure 4
Hypothesized mechanistic explanation of the interaction between P2 promoter and COMT coding region haplotypes. (A) In presence of the COMT promoter P2 haplotype associated with low levels of COMT transcription, the effect of the haplotypes covering the coding region of COMT is prominent because of the steep dose-response curve; (B) In absence of the “low transcription” P2 haplotype the total enzymatic activity is shifted to the right so that the effect of the haplotypes in the coding gene region is reduced because of the flattened dose-response curve.

Similar articles

See all similar articles

Cited by 17 articles

See all "Cited by" articles

Publication types

MeSH terms

Substances

Feedback