The Associated of the Risk of IVIG Resistance in Kawasaki Disease with ZNF112 Gene and ZNF180 Gene in a Southern Chinese Population

Zhaojin Lu,1,&ast; Zepeng Zheng,1,&ast; Yufen Xu,1,&ast; Chenlu Wang,1 Yueling Lin,1 Kun Lin,1 LanYan Fu,1 Huazhong Zhou,1 Lei Pi,1 Di Che,1 Xiaoqiong Gu1,2 1Department 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; 2Department of Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Di Che, Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, Guangdong, People’s Republic of China, Tel/Fax +86-20-38076562, Email chedi@gwcmc.org Xiaoqiong Gu, Department of Clinical Biological Resource Bank, Department of Clinical Laboratory, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, Guangdong, People’s Republic of China, Tel/Fax +86-20-38076561, Email guxiaoqiong@gwcmc.orgBackground: Kawasaki disease (KD) was one of the most common primary vasculitis. IVIG resistance was associated with an increased risk of coronary artery aneurysm. Accumulating evidences demonstrated that inflammatory gene polymorphisms might play important roles in IVIG resistance, and zinc finger proteins were closely related to immune inflammation regulation, but the effect of ZNF112/rs8113807 and ZNF180/rs2571051 on IVIG resistance in KD patients has not been reported.Methods: A total of 996 KD patients were recruited, and the assay of TaqMan-real-time polymerase chain reaction was used for ZNF112/rs8113807 and ZNF180/rs2571051 genotyping. Odds ratio (OR) and 95% confidence interval (CI) were calculated for estimating the relationship between the polymorphisms of the both SNPs (ZNF112/rs8113807 and ZNF180/rs2571051) and the risk of IVIG resistance.Results: Both of the ZNF112/rs8113807 CC/TC genotype and the ZNF180/rs2571051 TT/CT genotype increased the risk of IVIG resistance in KD (rs8113807: CC vs TT: adjusted OR = 1.83, 95% CI = 1.06– 3.16, p = 0.0293; CC/TC vs TT adjusted: OR = 1.49, 95% CI = 1.10– 2.02, p = 0.0094. rs2571051: TT vs CC adjusted: OR = 2.64, 95% CI = 1.62– 4.29, p < 0.0001; TT/CT vs CC adjusted: OR = 2.14, 95% CI = 1.37– 3.37, p = 0.0009; TT vs CC/CT adjusted: OR = 1.66, 95% CI = 1.22– 2.27, p = 0.0014). Furthermore, the combinative analysis of risk genotypes in ZNF112/rs8113807 and ZNF180/rs2571051 showed that patients with two unfavorable genotypes were more likely to increase risk of IVIG resistance than those who carried with zero or one unfavorable genotypes (adjusted: OR = 1.68, 95% CI = 1.24– 2.27, p = 0.0008).Conclusion: Our findings enriched the genetic background of IVIG resistance risk in the KD development and suggested that the ZNF112/rs8113807 C-carrier and the ZNF180/rs2571051 T-carrier were associated with increased risk of IVIG resistance in KD patients in Chinese southern population.Keywords: Kawasaki disease, ZNF112/rs8113807, ZNF180/rs2571051, IVIG resistance, inflammatory gene, polymorphism