Murina Filippo, Fochesato Cecilia, Leo Chiara, Condorelli Giuseppe E, Rocchi Anna, Amitrano Sara, Napolioni Valerio, Savasi Valeria
Lower Genital Tract Disease Unit, V. Buzzi Hospital-University of the Study of Milan, Via Castelvetro 24-20124, Milan, Italy.
Laboratory of Genomics-Polo d'Innovazione di Genomica, Genetica e Biologia, Strada del Petriccio e Belriguardo 35-53100, Siena, Italy.
J Sex Med. 2025 Apr 8;22(3):483-490. doi: 10.1093/jsxmed/qdae201.
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.
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.
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.
The genomic predisposition to hormones and receptors levels, together with clinical endophenotypes, can support VBD diagnosis and personalized treatment of related pain condition.
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 < .05). Cases showed a genomic predisposition to higher levels of membrane-associated progesterone receptor component 1 compared to controls (P < .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 < .05); predicted genomic levels of prolactin and Neurometer data at 250 Hz (-2.15E-07; P < .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 < .05).
Introduction of polygenic risk scores evaluation in clinical practice can assist early diagnosis and personalized therapeutic treatment of VBD.
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.
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.
外阴痛是一种多因素疾病，在普通人群中影响7%-16%的育龄妇女；然而，对于这种复杂疾病的遗传学基础仍知之甚少。
在一项病例对照研究中比较激素和受体水平的多基因风险评分，以研究它们在外阴痛中的作用及其与临床表型的相关性。
我们的病例对照研究纳入了前庭痛（VBD）患者和健康女性。所有参与者均接受了前庭棉拭子试验，并对其进行了评估：盆底、前庭营养状况、超声前庭黏膜厚度和电流感觉阈值水平（神经仪CPT设备）。进行了浅层全基因组测序和多基因风险评分计算。应用线性回归模型预测病例组和对照组之间的基因组易感性是否存在显著差异，并研究多基因风险评分与临床内表型的关系。
招募了30名VBD女性和30名对照。病例组和对照组在体重指数、前庭黏膜厚度、前庭营养健康状况、盆底张力过高和疼痛敏感性方面存在显著差异（P < 0.05）。与对照组相比，病例组显示出基因组易感性导致膜相关孕酮受体成分1水平更高（P < 0.05）。在考虑临床内表型时，病例组的多基因风险评分与多项临床指标之间存在显著相关性：睾酮和雌激素受体的预测基因组水平与前庭黏膜厚度值（估计值分别为9.74E-09和9.16E-08；P < 0.05）；催乳素的预测基因组水平与250Hz时的神经仪数据（-2.15E-07；P < 0.05）；催乳素、膜相关孕酮受体成分2和盐皮质激素受体的预测基因组水平与5Hz时的神经仪数据（分别为-3.75E-07、-3.43E-07和-3.06E-07；P < 0.
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