Keizo Asami Institute (iLIKA), Federal University of Pernambuco, Recife 50670-901, Pernambuco, Brazil.
Genetics Postgraduate Program, Federal University of Pernambuco, Recife 50670-901, Pernambuco, Brazil.
Genes (Basel). 2022 Dec 2;13(12):2271. doi: 10.3390/genes13122271.
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.
免疫系统在骨稳态中起着关键作用，因此，在绝经后骨质疏松症（OP）的病理生理学中也起着关键作用，因为雌激素缺乏会诱导炎症小体并增加促炎细胞因子的产生，如 IL-1β 和 IL-18。NLRP3 炎症小体复合物基因与细胞和动物模型中的骨稳态有关。在这里，我们进行了一项关联研究，评估了炎症小体 NLRP3 途径基因（NLRP3、CARD8、CASP1、IL-18 和 IL-1β）中的 SNV（单核苷酸变体），以评估这些基因中的变体是否与绝经后妇女原发性 OP 的易感性有关。
我们使用 SNV 特异性 Taqman 探针对 196 名绝经后 OP 患者和 103 名健康对照进行基因分型。使用 SNPstats 和 GraphPad Prism 8 软件进行数据和统计分析。
我们显示 NLRP3 rs35829419 CA 基因型与腰椎骨密度（BMD）平均值较低之间存在关联（ = 0.001）；我们还观察到 IL-1β rs16944 AA 基因型与全髋关节 BMD 平均值较高之间存在关联（ = 0.009）。IL-1β rs16944 GG 与碱性磷酸酶（ALP）水平降低相关（ = 0.009），IL-18 rs1946519 AA 与维生素 D 水平降低相关（ = 0.018）。此外，OP 患者存在维生素 D 和甲状旁腺激素（PTH）缺乏。
NLRP3 炎症小体复合物 SNVs 与 OP 严重程度相关，可能表明这些基因参与骨代谢及其失调。
