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

Kai Guo,1 Lijuan Qiu,1 Yufen Xu,2 Xiaoqiong Gu,2 Linyuan Zhang,3 Kun Lin,3 Xiaohuan Wang,1 Shanshan Song,1 Yu Liu,1 Zijian Niu,1 Shuxuan Ma1 1Department of Transfusion Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 2Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Department of Clinical Lab, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Shuxuan MaDepartment of Transfusion Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health No. 56 Nan Lishi Road, Xi Cheng District, Beijing, 100045, People’s Republic of ChinaTel +86 10 59616422Email masxfwyy@sina.comBackground: 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.Keywords: Kawasaki disease, rs7248320, AC008392.1, CARD8, lncRNA, single-nucleotide polymorphism