Prakriti and genetic profiling in Duchenne/Becker muscular dystrophy: An Ayurgenomic appraisal towards personalized...

Duchenne Muscular Dystrophy (DMD; OMIM #310200) and Becker Muscular Dystrophy (BMD; OMIM #300376) are rare and severe genetic conditions. These X-linked recessive Muscular Dystrophies (MDs) stem from variants in the DMD gene (OMIM #300377), encoding the dystrophin protein (Uniprot #P11532). The Prakriti concept, adjudged in Ayurveda, epitomizes an individual's nature-nurture and has gained significance in healthcare with the emerging field of Ayurgenomics.

The present research thoroughly analyses demographic, clinical, genetic, and Prakriti profiles in the D/BMD patients of Gujarat, India by integrating ancient wisdom with modern paradigms.

This observational study included 120 male participants whose demographic and clinical data were assessed. The concentration of total CPK was measured. Genetic analysis methods, viz. MPCR, MLPA, and NGS were applied to identify variants. Prakriti profiles of all participants were assessed using AyuSoft.

The demographic and clinical aspects of the study highlight the heterogeneity in disease severity and progression, with 15.83% of familial cases. The difference in CPK levels between DMD (12,445.15 U/L) and BMD (8,095 U/L) underscores the usual gradient in severity seen in these two types. Comprehensive genetic analysis revealed 87.5% DMD and 12.5% BMD, where 90% were identified as deletions, 4.17% duplications, and 5.83% point variants. In the cohort, 84.96% of variants were out-of-frame and 15.04% in-frame. Variant events were predominantly in distal regions (78.33%) and involved the central hotspot domain (65.83%). Among the detected deletions, 45-52 deletions exhibited dominantly in DMD participants with heightened frequency for exon 50. The study uniquely integrates Ayurvedic Prakriti profiles into the analysis, contributing additional insight into the disease framework. Based on seven distinct Prakritis, three profiles emerged prominently within our study. These are KaphapradhaanaPittaanubandhi (KP), KaphapradhaanaVaataanubandhi (KV), and VaatapradhaanaKaphaanubandhi (VK). The distribution of Prakriti differed between DMD and BMD participants. In both groups, 46.67% had KP Prakriti, whereas DMD had 40.95% KV and 12.38% VK. Conversely, 53.33% of BMD participants had KV Prakriti, and VK Prakriti was absent.

The varying distribution of profiles introduces possibilities for Prakriti-based stratification of D/BMD. The multiple Factor Analysis (MFA) highlights the importance of age and Severity in the analysis. Such integrative Ayurgenomics holds promise for a deeper comprehension of genetic conditions and for paving the way for the development of innovative, real-time, and personalized management.