The NLRP3 inflammasome rs35829419 C>A polymorphism is associated with type 2 diabetes mellitus in Saudi Arabia

Objectives: To investigate the frequency of NLRP3 gene rs35829419 C>A single-nucleotide polymorphism (SNP) in a Saudi Arabian population from Jazan (Southwest Saudi Arabia) and test its potential association with type 2 diabetes mellitus (T2DM).

Methods: This case-control study included 546 volunteers (271 patients with T2DM and 275 healthy controls) recruited from outpatient clinics at Jazan University Hospital and King Fahad Central Hospital in Jazan, Saudi Arabia, between December 2021 and July 2022. Genomic DNA was extracted from all samples and genotyped for the NLRP3 rs35829419 C>A SNP using TaqMan technology. The association between the NLRP3 rs35829419 polymorphism and T2DM was examined using logistic regression analysis.

Results: Overall genotype distributions were 90.5% (CC), 9.3% (CA), and 0.2% (AA). The heterozygous CA genotype was more frequent in T2DM group (12.2%) compared to the control group (6.5%) and logistic regression analysis showed a statically significant association with T2DM risk under codominant (CA versus CC; odds ratio [OR]=1.99; 95% confidence interval [CI]= [1.11-3.61]; p=0.0270), and dominant (CA+AA versus CC; OR=2.05; CI=[1.16-3.75]; p=0.019) models of inheritance.

Conclusion: This study revealed the frequency of NLRP3 rs35829419 C>A polymorphism in our population and showed a direct correlation between having the minor allele for A and having a higher risk of developing T2DM. This study highlights the significance of NLRP3 rs35829419 C>A polymorphism in the pathophysiology of T2DM.