Systematic confirmation study of GWAS-identified genetic variants for Kawasaki disease in a Chinese population.

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.

The roles of Ca2+/NFAT signaling genes in Kawasaki disease: single- and multiple-risk genetic variants.

Ca(2+)/nuclear factor of activated T-cells (Ca(2+)/NFAT) signaling pathway may play a crucial role in Kawasaki disease (KD). We investigated 16 genetic variants, selected by bioinformatics analyses or previous studies, in 7 key genes involved in this pathway in a Chinese population. We observed a significantly or marginally increased KD risk associated with rs2720378 GC + CC genotypes (OR = 1.39, 95% CI = 1.07-1.80, P = 0.014) or rs2069762 AC + CC genotypes (OR = 1.28, 95% CI = 0.98-1.67, P = 0.066), compared with their wild type counterparts. In classification and regression tree analysis, individuals carrying the combined genotypes of rs2720378 GC or CC genotype, rs2069762 CA or CC genotype and rs1561876 AA genotype exhibited the highest KD risk (OR = 2.12, 95% CI = 1.46-3.07, P < 0.001), compared with the lowest risk carriers of rs2720378 GG genotype. Moreover, a significant dose effect was observed among these three variants (Ptrend < 0.001). In conclusion, this study implicates that single- and multiple-risk genetic variants in this pathway might contribute to KD susceptibility. Further studies on more comprehensive single nucleotide polymorphisms, different ethnicities and larger sample sizes are warranted, and the exact biological mechanisms need to be further clarified.

8p22-23-rs2254546 as a susceptibility locus for Kawasaki disease: a case-control study and a meta-analysis.

8p22-23-rs2254546 was firstly discovered to be associated with Kawasaki disease (KD) susceptibility by a genome-wide association study. However, only one Chinese replication study has been performed so far. To verify this association in another Chinese population, a hospital-based case-control study in Zhejiang province was conducted followed by an integrated meta-analysis, comprising five case-control studies of 1958 cases, 5615 controls and four transmission disequilibrium tests of 503 trios. In our case-control study, significant associations were observed between GG genotype or GG/GA genotypes of rs2254546 and increased KD risk (OR = 1.86, 95% CI = 1.01-3.41, P = 0.045; OR = 1.83, 95% CI = 1.01-3.33, P = 0.048), compared with AA genotype; however, no significant association was found in allelic model (OR = 1.20, 95% CI = 0.96-1.50, P = 0.117). The meta-analysis further revealed that the G allele was significantly associated with the increased KD risk without evidence of heterogeneity (OR = 1.55, 95% CI = 1.42-1.70, P < 0.001). In conclusion, rs2254546 polymorphism might significantly contribute to the risk of KD.

Genetic variant in SWI/SNF complexes influences hepatocellular carcinoma risk: a new clue for the contribution of chromatin remodeling in carcinogenesis.

Chromatin remodeling has been newly established as an important cancer genome characterization and recent exome and whole-genome sequencing studies of hepatocellular carcinoma (HCC) showed that recurrent inactivating mutations in SWI/SNF subunits involved in the molecular basis of hepatocarcinogenesis. To test the hypothesis that genetic variants in the key subunits of SWI/SNF complexes may contribute to HCC susceptibility, we systematically assessed associations of genetic variants in SWI/SNF complexes with HCC risk using a two-staged case-control study in Chinese population. A set of 24 single nucleotide polymorphisms (SNPs) in SWI/SNF complexes were examined in stage 1 with 502 HCC patients and 487 controls and three promising SNPs (SMARCA4 rs11879293, rs2072382 and SMARCB1 rs2267032) were further genotyped in stage 2 comprising 501 cases and 545 controls for validation. SMARCA4 rs11879293 presented consistently significant associations with the risk of HCC at both stages, with an OR of 0.73 (95% CI: 0.62-0.87) using additive model in combined analysis. Moreover, the decreased risk of HCC associated with SMARCA4 rs11879293 AG/AA was more evident among HBsAg positive individuals (OR = 0.47, 95% CI: 0.27-0.80) in combined analysis. The study highlighted the potential role of the SWI/SNF complexes in conferring susceptibility to HCC, especially modified HCC risk by HBV infection.