Association of NLRP3 Inflammasome rs10754558 Polymorphism with Type 2 Diabetes Mellitus and Its Complications: Clinical and Bioinformatics Study.

INTRODUCTION

The NLRP3 inflammasome is thought to be an important element in innate immunity; aberrant activation might be caused by many inflammatory conditions, including diabetes. The study aims to investigate the association of the NLRP3 inflammasome rs10754558 polymorphism with susceptibility to type 2 diabetes mellitus (T2DM) and its complications using clinical and bioinformatics.

METHODS

In this case control study, 250 T2DM cases and 150 matched-age and gender healthy subjects were genotyped for rs10754558. Clinical, biochemical, and inflammatory markers (NLRP3, IL-1β) were measured. Associations with complications assessed using logistic regression. In silico analyses were carried out to evaluate miRNA binding and pathway interactions.

RESULTS

T2DM cases had a significantly higher frequency of the rs10754558 C allele than controls (20.8% vs 13.3%, p = 0.007). Nephropathy/CVD were significantly associated with the CC genotype (83.3%, p < 0.001). Higher levels of NLRP3, IL-1β, FPG, and HbA1c (p < 0.05) were observed in GC/CC genotype carriers. The C allele alters predicted miRNA binding in the 3' UTR increase mRNA stability. PPI network pathway enrichment highlighted the central roles of NLRP3 in IL-1β signaling.

CONCLUSION

The NLRP3 rs10754558 C allele was associated with higher risk of T2DM and vascular complications in Saudi patients and correlated with elevated NLRP3 and IL-1β levels. These population-specific findings highlight the biological relevance of the NLRP3-IL-1β axis in metabolic inflammation and provide a foundation for future functional and clinical studies.