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.