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AuthorGuaraná, Werbson Lima
AuthorLima, Camilla Albertina Dantas
AuthorBarbosa, Alexandre Domingues
AuthorCrovella, Sergio
AuthorSandrin-Garcia, Paula
Available date2022-12-29T05:58:16Z
Publication Date2022
Publication NameGenes
Identifierhttp://dx.doi.org/10.3390/genes13122271
CitationGuaraná, W.L.; Lima, C.A.D.; Barbosa, A.D.; Crovella, S.; Sandrin-Garcia, P. Can Polymorphisms in NLRP3 Inflammasome Complex Be Associated with Postmenopausal Osteoporosis Severity? Genes 2022, 13, 2271. https://doi.org/10.3390/genes13122271
URIhttp://hdl.handle.net/10576/37771
AbstractThe 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.
SponsorThis research was funded by the following Brazilian research agencies: CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nivel Superior) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico).
Languageen
PublisherMDPI
SubjectNLRP3
bone mineral density
inflammasome
osteoporosis
single-nucleotide variants
vitamin D
TitleCan Polymorphisms in NLRP3 Inflammasome Complex Be Associated with Postmenopausal Osteoporosis Severity?
TypeArticle
Issue Number12
Volume Number13
ESSN2073-4425
dc.accessType Open Access


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