Can Polymorphisms in NLRP3 Inflammasome Complex Be Associated with Postmenopausal Osteoporosis Severity?

Abstract

The immune system plays a critical role in bone homeostasis and, consequently, in the pathophysiology of postmenopausal osteoporosis (OP) since estrogen deficiency induces the inflammasome and increases production of pro-inflammatory cytokines, such as IL-1β and IL-18. NLRP3 inflammasome complex genes have been related with bone homeostasis in cellular and animal models. Here, we performed an association study evaluating SNVs (single-nucleotide variants) in inflammasome NLRP3 pathway genes (NLRP3, CARD8, CASP1, IL-18, and IL-1β) to assess whether variants in these genes could be related to susceptibility to primary OP in postmenopausal women. Methods: We genotyped 196 postmenopausal OP patients and 103 healthy controls using SNV-specific Taqman® probes. Data and statistical analyses were performed using the SNPstats and GraphPad Prism 8 software. Results: We showed an association between NLRP3 rs35829419 CA genotype and lower bone mineral density (BMD) mean at the lumbar spine (p = 0.001); we also observed an association between IL-1β rs16944 AA genotype and higher BMD mean at the total hip (p = 0.009). The IL-1β rs16944 GG was associated with lower alkaline phosphatase levels (ALP) (p = 0.009), and the IL-18 rs1946519 AA was associated with lower vitamin D levels (p = 0.018). Additionally, OP patients presented deficient vitamin D and parathyroid hormone (PTH). Conclusions: The NLRP3 inflammasome complex SNVs were associated with OP severity, possibly indicating these genes’ participation in bone metabolism and its dysregulation.