{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T19:27:51Z","timestamp":1780601271195,"version":"3.54.1"},"reference-count":38,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T00:00:00Z","timestamp":1669939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CAPES (Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de Nivel Superior)"},{"name":"CNPq (Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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-1\u03b2 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-1\u03b2) 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\u00ae 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-1\u03b2 rs16944 AA genotype and higher BMD mean at the total hip (p = 0.009). The IL-1\u03b2 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\u2019 participation in bone metabolism and its dysregulation.<\/jats:p>","DOI":"10.3390\/genes13122271","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T03:55:37Z","timestamp":1669953337000},"page":"2271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Can Polymorphisms in NLRP3 Inflammasome Complex Be Associated with Postmenopausal Osteoporosis Severity?"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1806-5219","authenticated-orcid":false,"given":"Werbson Lima","family":"Guaran\u00e1","sequence":"first","affiliation":[{"name":"Keizo Asami Institute (iLIKA), Federal University of Pernambuco, Recife 50670-901, Pernambuco, Brazil"},{"name":"Genetics Postgraduate Program, Federal University of Pernambuco, Recife 50670-901, Pernambuco, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla Albertina Dantas","family":"Lima","sequence":"additional","affiliation":[{"name":"Keizo Asami Institute (iLIKA), Federal University of Pernambuco, Recife 50670-901, Pernambuco, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre Domingues","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Clinical Hospital, Federal University of Pernambuco (UFPE), Recife 50740-900, Pernambuco, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8493-1168","authenticated-orcid":false,"given":"Sergio","family":"Crovella","sequence":"additional","affiliation":[{"name":"Biological Sciences Program, Department of Biological and Environmental Sciences, College of Arts and Sciences, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4641-7429","authenticated-orcid":false,"given":"Paula","family":"Sandrin-Garcia","sequence":"additional","affiliation":[{"name":"Keizo Asami Institute (iLIKA), Federal University of Pernambuco, Recife 50670-901, Pernambuco, Brazil"},{"name":"Department of Genetics, Federal University of Pernambuco, Recife 50670-901, Pernambuco, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1016\/S0140-6736(02)08657-9","article-title":"Osteoporosis I: Epidemiology and outcomes of osteoporotic fractures","volume":"359","author":"Cummings","year":"2002","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"882241","DOI":"10.3389\/fendo.2022.882241","article-title":"The Global Burden of Osteoporosis, Low Bone Mass, and Its Related Fracture in 204 Countries and Territories, 1990\u20132019","volume":"13","author":"Shen","year":"2022","journal-title":"Front. 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