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Localized Provoked Vulvodynia

Association With Nerve Growth Factor and Transient Receptor Potential Vanilloid Type 1 Genes Polymorphisms

Kalfon, Limor, PhD1; Azran, Audrey, MD2; Farajun, Yaniv, MD2; Golan-Hamu, Oshrat, MSc1; Toben, Aylah, MSc1; Abramov, Liora, MD3; Yeshaya, Arie, MD4; Yakir, Orly, MSc5; Zarfati, Doron, MD2; Falik Zaccai, Tzipora C., MD1,6; Bornstein, Jacob, MD, MPA2,6

Journal of Lower Genital Tract Disease: January 2019 - Volume 23 - Issue 1 - p 58–64
doi: 10.1097/LGT.0000000000000445
Original Research Articles: Vulva and Vagina

Objective The aim of the study was to study the associations between localized provoked vulvodynia (LPV) and several single-nucleotide polymorphisms (SNPs) in the transient receptor potential vanilloid type 1 (TRPV1), nerve growth factor (NGF), and the heparanase (HPSE) genes.

Materials and Methods Prevalence of SNPs among 65 women with moderate or severe primary LPV (initial symptoms occur with first provoking physical contact) and 126 healthy, ethnically matched controls was analyzed in an observational case-control study. Each participant answered a questionnaire addressing familial LPV occurrence and comorbid pain conditions.

Results Familial occurrences of LPV, temporomandibular joint (TMJ) symptoms, recurrent vaginitis, and irritable bowel syndrome were significantly higher among LPV women than healthy controls. Genotyping analyses revealed a novel, statistically significant high prevalence of polymorphism c.945G>C (rs222747) of TRPV1 and a SNP in the promoter region of NGF (rs11102930) in LPV women compared with controls. A logistic regression model for rs222747 and rs11102930 frequent alleles indicates significant LPV association within the entire study group and Ashkenazi Jewish women, respectively. Comparison of pain conditions with frequent alleles showed the rs222747 “CC” genotype of TRPV1 associated with women with TMJ, recurrent vaginitis, and LPV.

Conclusions Our results suggest novel genetic susceptibility to primary LPV associated with specific alleles in genes TRPV1 and NGF and propose the rs222747 “C” allele of TRPV1 as a common genetic predisposition for other pain syndromes.

1Institute of Human Genetics, Galilee Medical Center, Nahariya, Israel;

2Department of Obstetrics & Gynecology, Galilee Medical Center, Nahariya, Israel;

3Lis Maternity Hospital Tel Aviv Medical Center, Tel Aviv, Israel;

4Shnaider Women's Hospital, Beilinson Medical Center, Petah-Tikva, Israel;

5Statistics Unit, Galilee Medical Center, Nahariya, Israel; and

6The Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel

Reprint requests to: Jacob Bornstein, MD, Obstetrics and Gynecology, Galilee Medical Center, PO Box 21, Nahariya 22100, Israel. E-mail:; Tzipora Falik Zaccai, MD, Institute of Human Genetics, Galilee Medical Center, PO Box 21, Nahariya 22100, Israel. E-mail:

The authors have declared they have no conflicts of interest.

The grant for the study was awarded by the National Vulvodynia Association to T.C.F.Z. and J.B. The study was also supported by Galilee Medical Center.

T.C.F.Z. and J.B. contributed equally to this study.

The review board status was approved by the Israeli Review Board (Helsinki Committee). CLINICAL TRIAL REGISTRATION: NCT01664962.

Copyright © 2019 by the American Society for Colposcopy and Cervical Pathology