Lou Jiao, Zhong Rong, Shen Na, Lu Xu-zai, Ke Jun-tao, Duan Jia-yu, Qi Yan-qi, Wang Yu-jia, Zhang Qing, Wang Wei, Gong Fang-qi, Miao Xiao-ping
Department of Epidemiology and Biostatistics and Key Laboratory of Environment and Health, Ministry of Education &Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Guangdong Women and Children Hospital, Guangzhou, PR China.
Sci Rep. 2015 Feb 3;5:8194. doi: 10.1038/srep08194.
Genome-wide association studies (GWASs) have identified multiple single nucleotide polymorphisms (SNPs) associated with Kawasaki disease (KD). In this study, we replicated the associations of 10 GWAS-identified SNPs with KD in a Han Chinese population. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression, and cumulative effect of non-risk genotypes were also performed. Although none of the SNPs reached the corrected significance level, 4 SNPs showed nominal associations with KD risk. Compared with their respective wild type counterparts, rs1801274 AG+GG genotypes and rs3818298 TC+CC genotypes were nominally associated with the reduced risk of KD (OR = 0.77, 95% CI = 0.59-0.99, P = 0.045; OR = 0.74, 95% CI = 0.56-0.98, P = 0.038). Meanwhile, rs1801274 GG genotype, rs2736340 CC genotype or rs4813003 TT genotype showed a reduced risk trend (OR = 0.57, 95% CI = 0.35-0.93, P = 0.024; OR = 0.46, 95% CI = 0.26-0.83, P = 0.010; OR = 0.64, 95% CI = 0.43-0.94, P = 0.022), compared with rs1801274 AG+AA genotypes, rs2736340 CT+TT genotypes or rs4813003 TC+CC genotypes, respectively. Furthermore, a cumulative effect was observed with the ORs being gradually decreased with the increasing accumulative number of non-risk genotypes (Ptrend<0.001). In conclusion, our study suggests that 4 GWAS-identified SNPs, rs2736340, rs4813003, rs3818298 and rs1801274, were nominally associated with KD risk in a Han Chinese population individually and jointly.
全基因组关联研究（GWAS）已鉴定出多个与川崎病（KD）相关的单核苷酸多态性（SNP）。在本研究中，我们在汉族人群中重复验证了10个通过GWAS鉴定的SNP与KD的关联性。通过逻辑回归计算优势比（OR）和95%置信区间（CI），并对非风险基因型的累积效应进行了分析。尽管没有一个SNP达到校正后的显著性水平，但有4个SNP显示出与KD风险的名义关联性。与各自的野生型对应物相比，rs1801274的AG + GG基因型和rs3818298的TC + CC基因型与KD风险降低名义上相关（OR = 0.77，95% CI = 0.59 - 0.99，P = （此处原文有误，推测应为0.045）；OR = 0.74，95% CI = 0.56 - 0.98，P = 0.038）。同时，与rs1801274的AG + AA基因型、rs2736340的CT + TT基因型或rs4813003的TC + CC基因型相比，rs1801274的GG基因型、rs2736340的CC基因型或rs4813003的TT基因型显示出风险降低趋势（OR = 0.57，95% CI = 0.35 - 0.93，P = 0.024；OR = 0.46，95% CI = 0.26 - 0.83，P = 0.010；OR = 0.64，95% CI = 0.43 - 0.94，P = 0.022）。此外，观察到随着非风险基因型累积数量的增加，OR逐渐降低，存在累积效应（Ptrend<0.001）。总之，我们的研究表明，4个通过GWAS鉴定的SNP，即rs2736340、rs4813003、rs3818298和rs1801274，在汉族人群中单独和联合起来都与KD风险名义上相关。
