Evaluation of polygenic risk scores for hormones and receptors levels in patients with vestibulodynia: a case–control study
Authors: Murina Filippo , Fochesato Cecilia , Leo Chiara , Condorelli Giuseppe E , Rocchi Anna , Amitrano Sara , Napolioni Valerio , Savasi Valeria 
Published: December 2024

Abstract

Background
Vulvodynia is a multifactorial disease affecting 7%–16% of reproductive-aged women in general population; however, little is still known about the genetics underlying this complex disease.

Aim
To compare polygenic risk scores for hormones and receptors levels in a case–control study to investigate their role in vulvodynia and their correlation with clinical phenotypes.

Methods
Our case–control study included patients with vestibulodynia (VBD) and healthy women. All participants underwent a vestibular cotton swab test and the assessment of their: pelvic floor, vestibular trophism, ultrasound vestibular mucosa thickness, and current perception threshold levels (Neurometer CPT device). Shallow whole genome sequencing and polygenic risk score calculations were performed. Linear regression models were applied to predict whether genomic predisposition varied significantly between cases and controls, and to investigate the relationship of polygenic risk scores with clinical endophenotypes.

Outcomes
The genomic predisposition to hormones and receptors levels, together with clinical endophenotypes, can support VBD diagnosis and personalized treatment of related pain condition.

Results
Thirty women with VBD and 30 controls were recruited. Significant differences between cases and controls were observed for body mass index, vestibular mucosa thickness, vestibular trophic health, pelvic floor hypertone and pain sensitivity (P &lt; .05). Cases showed a genomic predisposition to higher levels of membrane-associated progesterone receptor component 1 compared to controls (P &lt; .05). When considering the clinical endophenotypes, cases showed significant correlations between their polygenic risk scores with several clinical measures: predicted genomic levels of testosterone and estrogen receptor and the vestibular mucosa thickness values (estimates: 9.74E-09 and 9.16E-08, respectively; P &lt; .05); predicted genomic levels of prolactin and Neurometer data at 250 Hz (-2.15E-07; P &lt; .05); predicted genomic levels of prolactin, membrane-associated progesterone receptor component 2 and mineralocorticoid receptor and Neurometer data at 5 Hz (-3.75E-07, -3.43E-07 and -3.06E-07, respectively; P &lt; .05).

Clinical Implications
Introduction of polygenic risk scores evaluation in clinical practice can assist early diagnosis and personalized therapeutic treatment of VBD.

Strengths and Limitations
Polygenic risk scores and clinical data allowed the identification of disease endophenotypes and highlighted the possibility of a personalized therapeutic approach. As limitations, these data should be confirmed on a larger cohort and polygenic risk score calculation should be adapted to ancestries other than European.

Conclusion
Cases showed significant differences compared to controls on both clinical and genetic data and specific endophenotypes necessary to classify disease development and treatment were identified.