Impact of genetic variation in interleukin-1 receptor antagonist and melanocortin-1 receptor genes on vulvar vestibulitis syndrome

J Reprod Med. 2004 Jul;49(7):503-9.


Objective: To investigate the risk of vulvar vestibulitis syndrome (VVS) in the presence of specific genetic variants (polymorphisms) that affect chronic inflammation, pain and skin color.

Study design: For a retrospective, case-control study performed at a university-based ambulatory gynecologic service, 36 consecutive VVS cases and 69 consecutive pain-free controls were selected. Polymerase chain reaction products containing genetic variants of 2 genes, the interleukin-1 receptor antagonist (IL1RN) and melanocortin-1 receptor (MC1R), were analyzed by 2 independent techniques, gel electrophoresis and direct sequencing.

Results: VVS cases were significantly more likely to be homozygous (+/+) for allele 2 of IL1RN as compared to controls (OR=4.4, 95% CI 1.11-17.14, P=.032). VVS cases were more likely to carry at least 1 of 6 loss-of-function polymorphisms of the MC1R gene as compared to controls, overall (OR=3.5, 95% CI 1.45-8.37, P=.005) and adjusted for race (OR=2.6, 95% CI 1.06-6.51, P=.037). The combined presence of allele 2 (+/+) IL1RN and at least 1 of the 6 MC1R polymorphisms resulted in an additive risk for VVS (OR=8.5; additive risk for VVS (OR=8.5; P=.046).

Conclusion: The risk of VVS is increased with proinflammatory genetic variants of IL1RN and MC1R, and combined genetic effects are associated with additive risk. This study supports a genetic contribution to VVS, suggests an increased risk of VVS in women withfair skin and indicates potential new treatment and primary prevention options.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Pain / etiology
  • Polymorphism, Genetic
  • Receptor, Melanocortin, Type 1 / genetics*
  • Retrospective Studies
  • Sialoglycoproteins / genetics*
  • Vulvar Diseases / complications
  • Vulvar Diseases / genetics*


  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Receptor, Melanocortin, Type 1
  • Sialoglycoproteins