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

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    NRLP3 osteoporosis (1.037Mb)
    Date
    2022
    Author
    Guaraná, Werbson Lima
    Lima, Camilla Albertina Dantas
    Barbosa, Alexandre Domingues
    Crovella, Sergio
    Sandrin-Garcia, Paula
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    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. 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. We showed an association between NLRP3 rs35829419 CA genotype and lower bone mineral density (BMD) mean at the lumbar spine ( = 0.001); we also observed an association between IL-1β rs16944 AA genotype and higher BMD mean at the total hip ( = 0.009). The IL-1β rs16944 GG was associated with lower alkaline phosphatase levels (ALP) ( = 0.009), and the IL-18 rs1946519 AA was associated with lower vitamin D levels ( = 0.018). Additionally, OP patients presented deficient vitamin D and parathyroid hormone (PTH). The NLRP3 inflammasome complex SNVs were associated with OP severity, possibly indicating these genes' participation in bone metabolism and its dysregulation.
    DOI/handle
    http://dx.doi.org/10.3390/genes13122271
    http://hdl.handle.net/10576/37771
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    • Biological & Environmental Sciences [‎931‎ items ]

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