Potential role of NLRP3 genetic polymorphism and gene expression in differentiating causes of neonatal cholestasis

It has long been a focus of research to differentiate among the various causes of neonatal cholestasis, particularly biliary atresia (BA) from non-BA. The NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome's role in the pathophysiology of BA is becoming increasingly clear. However, animal models served as the foundation for most of this research. As it is important to diagnose BA as early as possible for a favorable prognosis, the current investigation aimed to investigate the function of NLRP3 rs10754558 and NLRP3 gene expression level in distinguishing BA from non-BA.

The study included 21 patients with BA, 24 patients with neonatal cholestasis due to causes other than BA, and 20 healthy infants as the control group. A clinical evaluation and standard laboratory testing were conducted on each participant. NLRP3 rs10754558 and NLRP3 gene expression level were measured using TaqMan allelic discrimination assay and quantitative real-time polymerase chain reaction (PCR), respectively.

A significant difference in NLRP3 rs10754558 was observed between the BA and non-BA groups in the general genotype model (p = 0.048) and the overdominant model (p = 0.012). However, there was no discernible variation in the levels of NLRP3 gene expression between the two groups. In non-BA patients, there was a negative association between the international normalized ratio (INR) and expression of the NLRP3 gene. No correlation was found between NLRP3 expression and liver inflammation and fibrosis, nor between NLRP3 rs10754558 and NLRP3 expression.

In conclusion, NLRP3 rs10754558 may contribute to non-BA neonatal cholestasis in ways other than by influencing gene expression levels. However, in non-BA patients, NLRP3 expression levels may improve coagulation.