Oral potentially malignant disorders impact the oral mucosa and elevate the risk of oral cancer. In India, the high prevalence of oral submucous fibrosis and leukoplakia is attributed to habits such as tobacco use and smoking. Plasminogen activator inhibitor-1 plays a crucial role in cancer progression. Single-nucleotide polymorphisms are the most widespread genetic variations associated with various diseases, including cancers. This study aimed to investigate the association between PAI-1 promoter rs2227631 (- 844G > A) and missense variant rs6092 (+ 43G > A) polymorphisms and the susceptibility to OSMF and leukoplakia in a South Indian cohort of chewers and smokers. The rs2227631 and rs6092 of PAI-1 were analysed using PCR- RFLP in 285 subjects including OSMF, leukoplakia and healthy controls, along with their habitual factors. The allele frequencies and genotypic associations were examined. The impact of these SNPs on mRNA secondary structure, gene-gene and protein-protein interactions was also analysed using in silico tools. The habits of chewers and smokers were (79% and 72%) in OSMF and (62% and 75%) in leukoplakia and disease prevalent was (78% and 59%) males and (22% and 26%) females respectively. The G allele of rs2227631 and A allele of rs6092 were significantly associated with the diseases (P < 0.05). PAI-1 polymorphisms rs2227631 and rs6092 were associated with OSMF and leukoplakia of the south Indian cohort.
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