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Detangling red hair from pain: phenotype-specific contributions from different genetic variants in melanocortin-1 receptor.

Publication ,  Journal Article
Zorina-Lichtenwalter, K; Maixner, W; Diatchenko, L
Published in: Pain
May 2020

Genetic variation in melanocortin-1 receptor (MC1R) has a known role in red hair. Studies on responses to noxious stimuli in red-haired individuals have also been conducted, with mixed findings. To investigate a possible divergence between variants responsible for red hair and pain sensitivity, we performed a genewide association analysis in the Orofacial Pain: Prospective Evaluation and Risk Assessment cohort. All genotyped (17) MC1R variants were tested for association with heat pain temporal summation and sensitivity. Our analyses showed an association for pain sensitivity with the 5'-UTR, tagged by rs3212361, and 1 missense variant, rs885479 (R163Q), previously shown to be weakly associated with red hair. For both variants, the minor allele was protective. These results were validated in the 500,000-person UK Biobank cohort, where the minor alleles of rs3212361 and rs885479 were associated with a reduced count of persistent pain conditions as well as individual pain conditions. Haplotype association analysis revealed a possible joint effect from the 2 individual variants. The 5'-UTR variant rs3212361 was further identified as an expression quantitative trait locus, associated with reduced transcript levels of MC1R in the brain and in the peripheral tibial nerve. Hair colour association analysis of the loss-of-function 5'-UTR rs3212361 allele identified association with red hair, and red hair colour itself was associated with a reduced count of persistent pain conditions. Together, our results suggest that primarily different mechanisms-affecting expression levels vs protein activity-mediated by different genetic variants in the MC1R locus contribute to red hair and pain.

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Published In

Pain

DOI

EISSN

1872-6623

Publication Date

May 2020

Volume

161

Issue

5

Start / End Page

938 / 948

Location

United States

Related Subject Headings

  • Receptor, Melanocortin, Type 1
  • Prospective Studies
  • Phenotype
  • Pain
  • Male
  • Humans
  • Hair Color
  • Genetic Variation
  • Female
  • Anesthesiology
 

Citation

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Zorina-Lichtenwalter, K., Maixner, W., & Diatchenko, L. (2020). Detangling red hair from pain: phenotype-specific contributions from different genetic variants in melanocortin-1 receptor. Pain, 161(5), 938–948. https://doi.org/10.1097/j.pain.0000000000001780
Zorina-Lichtenwalter, Katerina, William Maixner, and Luda Diatchenko. “Detangling red hair from pain: phenotype-specific contributions from different genetic variants in melanocortin-1 receptor.Pain 161, no. 5 (May 2020): 938–48. https://doi.org/10.1097/j.pain.0000000000001780.
Zorina-Lichtenwalter, Katerina, et al. “Detangling red hair from pain: phenotype-specific contributions from different genetic variants in melanocortin-1 receptor.Pain, vol. 161, no. 5, May 2020, pp. 938–48. Pubmed, doi:10.1097/j.pain.0000000000001780.
Zorina-Lichtenwalter K, Maixner W, Diatchenko L. Detangling red hair from pain: phenotype-specific contributions from different genetic variants in melanocortin-1 receptor. Pain. 2020 May;161(5):938–948.

Published In

Pain

DOI

EISSN

1872-6623

Publication Date

May 2020

Volume

161

Issue

5

Start / End Page

938 / 948

Location

United States

Related Subject Headings

  • Receptor, Melanocortin, Type 1
  • Prospective Studies
  • Phenotype
  • Pain
  • Male
  • Humans
  • Hair Color
  • Genetic Variation
  • Female
  • Anesthesiology