Single-Nucleotide Polymorphism LncRNA AC008392.1/rs7248320 in CARD8 is Associated with Kawasaki Disease Susceptibility in the Han Chinese Population

Abstract

Background Kawasaki disease (KD) is a multisystem vasculitis in infants and young children and involved in the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome activation. Genetic factors may increase the risk of KD. To assess the association between rs7248320 in long noncoding RNA (lncRNA) AC008392.1 located in the upstream region of CARD8 and the risk of KD, a case–control study was conducted in the Han Chinese population. Methods This study genotyped the polymorphism rs7248320 in the lncRNA AC008392.1 gene using the TaqMan real-time polymerase chain reaction assay. The genetic contribution of rs7248320 was evaluated using odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. The association between rs7248320 and KD susceptibility was analyzed by performing a hospital-based case–control study including 559 KD patients and 1055 non-KD controls. Results In this study, a significant relationship between rs7248320 and KD risk was observed in the genotype/allele frequency distribution. The rs7248320 polymorphism was associated with a significantly decreased risk of KD after adjustment for age and sex (AG vs AA: adjusted OR = 0.80, 95% CI: 0.64–0.99, P = 0.0421; GG vs AA: adjusted OR = 0.71, 95% CI: 0.51–1.00, P = 0.0492; AG/GG vs AA: adjusted OR = 0.78, 95% CI: 0.63–0.96, P = 0.0186). Moreover, the rs7248320 G allele also exhibited a decreased risk for KD (adjusted OR = 0.83, 95% CI: 0.72–0.97, P = 0.0193) compared with the A allele. In the stratification analysis, compared to the rs7248320 AA genotype, AG/GG genotypes were more protective for males (OR = 0.71, 95% CI: 0.55–0.93, P = 0.0122). Conclusion This study suggests for the first time that the lncRNA AC008392.1 rs7248320 polymorphism may be involved in KD susceptibility in the Han Chinese population.

Efficacy of Glucocorticoid plus Intravenous Immunoglobulin in Children with Immunoglobulin-Insensitive Kawasaki Disease

“…Kawasaki disease (KD), a mucocutaneous lymph node syndrome named after its discoverer (Kawasaki), is an acute febrile inflammatory disease that tends to occur among infants and children [ 1 , 2 ]. KD is the most common cause of acquired heart disease in children in developed countries and even leads to coronary artery aneurysms (CAA), elevating the risk of coronary artery thrombosis in the later stage [ 3 ]. In addition, the main clinical presentations of KD include persistent fever, pleural rash, conjunctival congestion, oral mucosal lesions, swollen neck lymph nodes, and severe hand swelling, which seriously threaten children's physical and mental health [ 4 ].…”

A LncRNA gene polymorphism (rs1814343) is associated with the risk of coronary artery lesions in southern Chinese Kawasaki disease patients

“…The etiology of KD is still unclear, and many association studies have identified that the lncRNAs PINC, SOCS2-AS1, SRA, HCG22, MHRT and AC008392.1 may modify the occurrence of KD and may even be related to CAL complications. 24,[30][31][32] So far, no study report has explored the association of the lncRNA rs1814343 C > T polymorphism with the susceptibility to KD. Studies have shown that lncRNAs play major roles in cardiovascular disease because lncRNAs can regulate the development of cardiovascular disease by regulating the growth and function of vascular endothelium and the migration/ differentiation of vascular smooth muscle cells.…”

“…The etiology of KD is still unclear, and many association studies have identified that the lncRNAs PINC, SOCS2‐AS1, SRA, HCG22, MHRT and AC008392.1 may modify the occurrence of KD and may even be related to CAL complications 24,30–32 . So far, no study report has explored the association of the lncRNA rs1814343 C > T polymorphism with the susceptibility to KD.…”

Potential roles of NLRP3 inflammasome in the pathogenesis of Kawasaki disease

“…The long noncoding RNA (LncRNA) AC008392.1 gene is located in the long arm of chromosome 19 upstream of CARD8, and it is known that it expresses in several cell lines such as B cells and tumor cells (K. Guo et al, 2021; Lv et al, 2018; Yin et al, 2015). CARD8 is a component of the NLRP3 inflammasome that inhibits NLRP3 inflammasome activation, which is one of the main drivers of KD vasculitis (Takahashi, 2022; Wang et al, 2021).…”

“…Moreover, several studies have revealed the important link of CARD8 polymorphisms with inflammation‐related diseases such as rheumatoid arthritis (Kastbom et al, 2010), atopic dermatitis (Bivik et al, 2013), Crohn's disease (Z. T. Zhang et al, 2015), and gout (Y. Chen, Ren et al, 2015). Based on these shreds of information, K. Guo et al (2021) designed a case‐control study to investigate the association of rs7248320 in AC008392.1 and susceptibility to KD. They found that rs7248320 polymorphism significantly reduces the risk of KD after sex and age adjustment.…”