Epidemiological, clinical, and molecular studies on nail disorders in the human population of Punjab, Pakistan

Nail disorders in Pakistan are an underestimated burden, and no population-based molecular data on nail disorders in Punjab have been provided previously. The study aims to establish prevalence, clinical presentation, risk factors and genetic structure of nail disorders in ten districts. Methods and.

A cross-sectional survey (20,222,024) involved the recruitment of 1,240 affected participants and 480 controls. Diagnostics consisted of mycological culture, dermoscopy, histopathology, targeted NGS (NailGenome-94v2), and pharmacogenomic (CYP2C19, CYP3A4, ABCB1). The overall prevalence was 98.4/1,000 with a southern hotspot: Sadiqabad (127.6/1,000), Rahim Yar Khan (119.2/1,000) and Bahawalpur (112.8/1,000). Severe onychomycosis was predicted by agricultural occupation (aOR 2.14), pesticide exposure (aOR 1.98), and living in the south (aOR 2.87). In 17 Seraiki-speaking families, a novel FZD6 c.1757G > A (p.Arg586Gln) variant was identified, with shared haplotype evidence suggesting a possible founder effect; however, this interpretation requires confirmation in larger population-based and functional studies. The prevalence of a CYP2C19 poor metabolizer was 12.4% and was independently related to itraconazole hepatotoxicity (aOR 4.12).

The high burden of nail disease in Punjab appears to reflect occupational exposures, delayed diagnosis, and possible enrichment of hereditary nail-disorder variants in southern districts. In this group, pretreatment CYP2C19 screening would be justified to use systemic itraconazole.

Clinical trial number: not applicable.