Integrative Assessment of Genetic Variants and Ayurvedic Prakriti in Endometriosis Using Whole Exome Sequencing

Background: Endometriosis is defined by the presence of endometrial-like tissue outside of its usual location, which is the lining of the uterus. This Endometriosis is a complex gynaecological disorder with heterogeneous clinical presentations and poorly understood genetic underpinnings. Whole exome sequencing (WES) has enabled the discovery of novel variants associated with disease susceptibility and progression. Ayurveda, the traditional system of Indian medicine, classifies individuals into constitutional types or prakriti (Vata, Pitta, Kapha), which are hypothesized to influence disease predisposition and phenotypic variability. Prakriti is influenced by culture, inherited characteristics, and geographical origin. Objective: This study aimed to integrate WES-based genetic profiling with prakriti analysis in diagnosed cases of endometriosis to explore potential associations between constitutional types and genetic variants.Materials and Methods :This study was conducted on 50 clinically diagnosed cases of endometriosis at Sir Sunderlal Hospital, Institute of Medical Sciences, Banaras Hindu University (BHU), in collaboration with the Centre for Genetic Disorders, Institute of Science, BHU. Exome Analysis –The exome sequencing will be done illumine HiseqR NGS platform either through outsourcing or on the platform available in Centre for Genetic Disorders, BHU. Prakriti Assessment: Constitutional typing (prakriti) was performed using a validated questionnaire-based proforma, followed by expert clinical evaluation, classifying patients into Vata, Pitta, or Kapha predominance. Genetic Analysis: Peripheral blood samples were collected from all participants. Genomic DNA was extracted using the salting-out method. Next-generation sequencing (NGS) was performed to identify genetic variants, with subsequent bioinformatics analysis to annotate and prioritize genes associated with endometriosis. Clinical Correlates: In addition to genomic analysis, patient demographics and clinical profiles, including age, chief complaints, menstrual history, and endocrine parameters, were recorded and analyzed. Statistical Analysis: Correlation between prakriti types and genetic variations was assessed, along with associations with clinical parameters. Statistical significance was evaluated using chi-square. Results: Among the 50 endometriosis patients, prakriti distribution revealed a predominance of Vataja prakriti, followed by Pittaja prakriti, with minimal representation of Kaphaja type. NGS analysis demonstrated a higher burden of gene variations in Vataja prakriti individuals compared to other groups. Variants in genes implicated in endometriosis pathogenesis were particularly enriched in the Vataja subgroup, whereas Pitta-dominant patients exhibited moderate associations, and Kapha-dominant individuals showed minimal variations. Correlational analysis suggested a possible association between Vataja prakriti and genetic susceptibility to endometriosis. Additionally, clinical parameters such as menstrual irregularities and endocrine profile alterations were more frequent in Vataja patients, supporting a prakriti-linked predisposition. Conclusion:The integration of WES with prakriti analysis provides novel insights into the molecular and constitutional basis of endometriosis. This interdisciplinary approach may facilitate a more personalized framework for understanding disease heterogeneity and pave the way toward individualized management strategies combining genomic and Ayurvedic perspectives.