Interferon-stimulated gene 15 polymorphisms are associated with spontaneous preterm birth in Taiwanese women.

PROBLEM: Immune and inflammatory responses are known to be major causes of preterm birth (PTB). The maternal genetic background plays an important role in the development of PTB. Interferon-stimulated gene 15 (ISG15) is an interferon-induced protein which can modulate immune cell activation and function. We aim to study if polymorphisms in the ISG15 gene are associated with spontaneous PTB (sPTB) risk in Taiwanese women. METHOD OF STUDY: ISG15 rs4615788 C/G, rs1921 G/A, and rs8997 A/G polymorphisms were genotyped in a hospital-based study of 112 women with sPTB and 1120 term controls. The plasma concentrations of ISG15 were determined by enzyme-linked immunosorbent assay. RESULTS: We found the ISG15 rs1921 G-rs8997 A haplotype was associated with decreased risk for PTB (χ2  = 6.26, p = .01, pc  = .04). The A/G genotype of ISG15 rs8997 polymorphism might have the potential to confer reduced risk of PTB women (χ2  = 4.09, p = .04, pc  = .08). Spontaneous PTB women displayed higher plasma ISG15 levels compared to term controls (p < .001). The plasma ISG15 levels among pregnant women with rs8997 A/G genotype were found significantly lower compared to G/G genotype (p = .03). CONCLUSIONS: Women with the ISG15 rs1921 G-rs8997 A haplotype may associate with spontaneous PTB. These findings provide new insights into the etiology of preterm birth.

Validation of genome-wide associated variants for Kawasaki disease in a Taiwanese case-control sample.

Kawasaki disease (KD) is an acute febrile systemic vasculitis of unknown etiology that affects infants and young children. Considerable evidence supports the hypothesis that there is a genetic basis for KD susceptibility. Genome-wide association studies (GWAS) have identified several genetic variants associated with KD. This study aims to replicate three novel KD-associated single nucleotide polymorphisms (SNPs), identified by GWAS in Japanese, in a Taiwanese population. Associations between these SNPs and development of coronary artery lesions (CALs) were also investigated. The rs2254546 A/G, rs2857151 A/G, and rs4813003 C/T SNPs were genotyped in 681 children with KD and 563 ethnically-matched healthy controls using TaqMan Assay or DNA sequencing. We found rs2254546 and rs4813003 SNPs were significantly associated with KD (G allele, odds ratio [OR] = 1.54, P = 1.0 × 10-5; C allele, OR = 1.32, P = 8.1 × 10-4). However, no evidence for associations with CAL development was observed. Our study successfully validates associations of the rs2254546 and rs4813003 SNPs with KD in a Taiwanese population. Further functional studies of the SNPs are important in understanding the pathogenesis of KD.

Mutations in glucokinase and other genes detected in neonatal and type 1B diabetes patient using whole exome sequencing may lead to disease-causing changes in protein activity.

Monogenic diabetes is caused by mutations that reduce ß-cell function. While Sanger sequencing is the standard method used to detect mutated genes. Next-generation sequencing techniques, such as whole exome sequencing (WES), can be used to find multiple gene mutations in one assay. We used WES to detect genetic mutations in both permanent neonatal (PND) and type 1B diabetes (T1BD). A total of five PND and nine T1BD patients were enrolled in this study. WES variants were assessed using VarioWatch, excluding those identified previously. Sanger sequencing was used to confirm the mutations, and their pathogenicity was established via the literature or bioinformatic/functional analysis. The PND and T1BD patients were diagnosed at 0.1-0.5 and 0.8-2.7 years of age, respectively. Diabetic ketoacidosis was present at diagnosis in 60% of PND patients and 44.4% of T1BD patients. We found five novel mutations in five different genes. Notably, patient 602 had a novel homozygous missense mutation c.1295C > A (T432 K) in the glucokinase (GCK) gene. Compared to the wild-type recombinant protein, the mutant protein had significantly lower enzymatic activity (2.5%, p = 0.0002) and Vmax (1.23 ±â€¯0.019 vs. 0.33 ±â€¯0.016, respectively; p = 0.005). WES is a robust technique that can be used to unravel the etiologies of genetically heterogeneous forms of diabetes. Homozygous inactivating mutations of the GCK gene may have a significant role in PND pathogenesis.

Replication of results from a cervical cancer genome-wide association study in Taiwanese women.

Genetic epidemiological studies show that genetic factors contribute significantly to cervical cancer carcinogenesis. Several genome-wide association studies (GWAS) have revealed novel genetic variants associated with cervical cancer susceptibility. We aim to replicate 4 GWAS-identified single nucleotide polymorphisms (SNPs), which were associated with invasive cervical cancer in Chinese women, in a Taiwanese population. The rs13117307 C/T, rs8067378 A/G, rs4282438 G/T, and rs9277952 A/G SNPs were genotyped in 507 women with cervical squamous cell carcinoma (CSCC) and 432 age/sex matched healthy controls by using TaqMan PCR Assay. Human papillomavirus (HPV) DNA test and typing were performed in CSCC patients. Only the rs4282438 SNP was found to be significantly associated (G allele, odds ratio [OR] = 0.67, P = 1.5 × 10-5). This protective association remained in HPV-16 positive CSCC subgroup (G allele, OR = 0.60, P = 1.2 × 10-5). In conclusion, our study confirms the association of rs4282438 SNP with CSCC in a Taiwanese population. However, larger sample sets of other ethnic groups are required to confirm these findings.

ITPR3 gene haplotype is associated with cervical squamous cell carcinoma risk in Taiwanese women.

Host immunogenetic background plays an important role in human papillomavirus (HPV) infection and cervical cancer development. Inositol 1,4,5-triphosphate receptor type 3 (ITPR3) is essential for both immune activation and cancer pathogenesis. We aim to investigate if ITPR3 genetic polymorphisms are associated with the risk of cervical cancer in Taiwanese women. ITPR3 rs3748079 A/G and rs2229634 C/T polymorphisms were genotyped in a hospital-based study of 462 women with cervical squamous cell carcinoma (CSCC) and 921 age-matched healthy control women. The presence and genotypes of HPV in CSCC was determined. No significant association of individual ITPR3 variants were found among controls, CSCC, and HPV-16 positive CSCC. However, we found a significant association of haplotype AT between CSCC and controls (OR = 2.28, 95% CI 1.31-3.97, P = 2.83 × 10-3) and the OR increased further in CSCC patients infected with HPV-16 (OR = 2.89, 95% CI 1.55-5.37, P = 4.54 × 10-4). The linkage disequilibrium analysis demonstrated that ITPR3 association with CSCC was independent of HLA-DRB1 alleles. In conclusion, these findings suggest that AT haplotype in the ITPR3 gene may serve as a potential marker for genetic susceptibility to CSCC.

Functional variant of the P2X7 receptor gene is associated with human papillomavirus-16 positive cervical squamous cell carcinoma.

Human papillomavirus (HPV) infection and the fate of HPV infected cervical epithelial cells are strictly associated with cervical cancer development. P2X7 receptor has been implicated in both the regulation of immune responses and apoptosis of cervical cancer cells. The study aims to investigate if polymorphisms in the P2RX7 gene are associated with the risk of cervical cancer in Taiwanese women. P2RX7 253 T/C, 835 G/A, and 1513 A/C loss-of-function polymorphisms were genotyped in a hospital-based study of 507 women with cervical squamous cell carcinoma (CSCC) and 1619 age-matched healthy control women. The presence and genotypes of HPV in CSCC was determined. The frequency of 253 C/C genotype was found to increase significantly in patients with HPV-16 positive CSCC compared with controls (odds ratio = 10.2, 95% confidence interval 1.39-87.8, Pc = 0.03). No significant associations were found for other 2 polymorphisms. Analysis of haplotypes also revealed no significant differences among women with CSCC, those with HPV-16 positive CSCC and controls. In conclusion, inheritance of the C/C genotype at position 253 in the P2RX7 gene may contribute to the risk of HPV-16 associated CSCC in Taiwanese women.

Association of Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4) Gene Polymorphisms with Autoimmune Thyroid Disease in Children and Adults: Case-Control Study.

Autoimmune thyroid disease (AITD), including Graves disease (GD) and Hashimoto disease (HD), is an organ-specific autoimmune disease with a strong genetic component. Although the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) polymorphism has been reported to be associated with AITD in adults, few studies have focused on children. The aim of our study was to investigate whether the CTLA4 polymorphisms, including -318C/T (rs5742909), +49A/G (rs231775), and CT60 (rs3087243), were associated with GD and HD in Han Chinese adults and children. We studied 289 adult GD, 265 pediatric GD, 229 pediatric HD patients, and 1058 healthy controls and then compared genotype, allele, carrier, and haplotype frequencies between patients and controls. We found that CTLA4 SNPs +49A/G and CT60 were associated with GD in adults and children. Allele G of +49A/G was significantly associated with GD in adults (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.21-1.84; corrected P value [Pc] < 0.001) and children (OR, 1.42; 95% CI, 1.15-1.77; Pc = 0.002). Allele G of CT60 also significantly increased risk of GD in adults (OR, 1.63; 95% CI, 1.27-2.09; Pc < 0.001) and GD in children (OR, 1.58; 95% CI, 1.22-2.04; Pc < 0.001). Significant linkage disequilibrium was found between +49A/G and CT60 in GD and control subjects (D' = 0.92). Our results showed that CTLA4 was associated with both GD and HD and played an equivalent role in both adult and pediatric GD in Han Chinese population.

Genetic susceptibility to cervical squamous cell carcinoma is associated with HLA-DPB1 polymorphisms in Taiwanese women.

Cervical cancer is a multifactorial disease, and increasing evidence suggests that host immunogenetic background may contribute to its pathogenesis. Genetic variations in human leukocyte antigen (HLA) genes may alter the efficiency of immune response to human papillomavirus (HPV) antigens and have been implicated in the risk of cervical cancer. We investigated whether polymorphisms in the HLA-DPB1 gene were associated with cervical cancer risk in a Taiwanese population. HLA-DPB1 alleles and +550 G/A polymorphism were genotyped in a case-control study of 473 women with cervical squamous cell carcinoma (CSCC) and 676 healthy controls. The presence and genotypes of HPV in CSCC were determined. We found that the DPB1*05:01 and +550 A alleles were associated with decreased and increased risk of CSCC, respectively [odds ratio (OR) = 0.72, Pc = 0.001; OR = 1.25, Pc = 0.03]. In subgroup analysis based on HPV type 16 positivity, significant associations were shown in the DPB1*05:01 and *13:01 alleles (OR = 0.65, Pc = 0.0007; OR = 1.83, Pc = 0.004). Furthermore, the DPB1*05:01-G and *13:01-G haplotypes conferred decreased and increased risk of both CSCC and HPV-16 positive CSCC women, respectively (OR = 0.72, Pc = 0.0009; OR = 0.63, Pc = 0.0004 for DPB1*05:01-G; OR = 1.55, Pc = 0.03; OR = 1.84, Pc = 0.004 for DPB1*13:01-G). A risk haplotype DPB1*02:01-A was also observed in the HPV-16 positive CSCC women (OR = 1.51, Pc = 0.05). These findings suggest that HLA-DPB1 gene is involved in the CSCC development.

Human leucocyte antigen-G polymorphisms are associated with cervical squamous cell carcinoma risk in Taiwanese women.

BACKGROUND: The mere presence of human papillomavirus (HPV) is not enough for cervical cancer development and immunogenetic background may play an important role. Human leucocyte antigen (HLA)-G acts as a negative regulator of immune responses and its expression in tumour cells may enable them to avoid immune attack. We aim to study if polymorphisms in the HLA-G gene are associated with cervical cancer risk in Taiwanese women. METHODS: +1537 A/C, 14-bp deletion/insertion (Del/Ins), and +3142 G/C polymorphisms were genotyped in a hospital-based study of 317 women with cervical squamous cell carcinoma (CSCC) and 400 healthy control women frequency matched by age. The presence and genotypes of HPV in CSCC were determined. RESULTS: We found the +3142 C/C genotype and C allele were associated with increased risk for CSCC (adjusted odds ratio [OR]=1.78, P=0.004; adjusted OR=1.31, P=0.014, respectively). In subgroup analysis based on HPV type 16 positivity, significant associations with higher adjusted ORs were found in +3142 C/C genotype and C allele (adjusted OR=2.19, P=0.001; adjusted OR=1.48, P=0.003, respectively) and +1537 C/C genotype and C allele frequencies increased significantly (adjusted OR=2.88, P=0.004; adjusted OR=1.69, P=0.0005, respectively). Furthermore, the C-Del-C haplotype conferred increased risk of both CSCC and HPV-16 positive CSCC women (adjusted OR=1.41, P=0.009; adjusted OR=1.94, P=0.0001, respectively). CONCLUSION: These findings suggest that HLA-G gene is involved in the susceptibility to CSCC.

Genetic variants in interleukin-18 gene and risk for cervical squamous cell carcinoma.

Cervical cancer is strongly associated with infection of oncogenic types of human papillomavirus (HPV). However, HPV infection alone is not sufficient for progression to cervical cancer. It is now recognized that host immunogenetic background participates in the control of HPV infection and development of cervical cancer. Interleukin-18 (IL-18) is a multifunctional cytokine that induces interferon-gamma secretion and plays a central role in antitumor immunity. The aim of this study is to determine if potentially functional polymorphisms in IL-18 gene are associated with risk of HPV-induced cervical cancer in Taiwanese women. Pre-Developed TaqMan Allelic Discrimination Assay was used to genotype IL-18 -1297 T/C, -607 C/A, -380 C/G, -137 G/C, and +105 A/C polymorphisms in a hospital-based study of 470 women with cervical squamous cell carcinoma (CSCC) and 722 age-matched healthy control women. The presence and genotypes of HPV in CSCC was determined by PCR. None of the polymorphisms or any haplotype was found to have significant differences in distribution among all subjects with CSCC, those with HPV-16 positive CSCC, and controls. Our results suggest that the IL-18 -1297 T/C, -607 C/A, -380 C/G, -137 G/C, and +105 A/C polymorphisms are not associated with susceptibility to CSCC in Taiwanese women.

Gender-specific association of the interleukin 18 gene with symptomatic gallstone disease.

BACKGROUND AND AIM: Symptomatic gallstone disease (SGSD) induced several inflammatory responses and affected extrahepatic bile ducts. Although the pathology and environmental risk factors of gallstone disease are well documented, immune or inflammatory responses in SGSD development are still inconclusive. Interleukin 18 (IL18) is a pro-inflammatory cytokine that plays an important role in immune, infectious, and inflammatory diseases because of the induction of interferon-γ. In this study, we investigated whether polymorphisms of the IL18 gene were associated with SGSD susceptibility. METHODS: Genomic DNA was isolated from the whole blood samples of 445 patients with SGSD and 1121 gallstone-free controls. The IL18 rs549908T>G, rs5744247C>G, rs187238G>C, rs1946518T>G, and rs360719A>G polymorphisms were genotyped using predeveloped TaqMan allelic discrimination assay. RESULTS: We found IL18 rs5744247G allele conferred protection against SGSD in female patients (odds ratio = 0.75, corrected P-value = 0.015). Haplotype analysis revealed that TGGTA protected females from SGSD development (odds ratio = 0.75, corrected P-value = 0.02). CONCLUSIONS: Based on our findings, IL18 rs5744247C>G polymorphism could be a potential genetic marker to predict SGSD susceptibility in Han Chinese women.

The IL18 gene and Hashimoto thyroiditis in children.

Interleukin 18 (IL18) stimulates interferon-γ production in Th1 cells which are prominent in the thyroid of Hashimoto thyroiditis (HT). We investigated the association between the IL18 gene and HT. There were 116 children with HT and 1272 controls. rs187238 and rs1946518 in the promoter region of the IL18 gene were genotyped. Differences in genotype, allele, carrier, and haplotype distributions between patients and controls were compared. A Pc value <0.05 was considered significant. The frequency of the C/G genotype of rs187238 was significantly higher in patients and conferred a risk of HT (OR, 1.96; 95% CI, 1.30-2.95; Pc, 0.0021). So did the frequencies of allele C (OR, 1.73; 95% CI, 1.22-2.44; Pc, 0.0035) and carrier C (OR, 1.96; 95% CI, 1.31-2.92; Pc, 0.0017), however the frequency of the G/G genotype was significantly lower in patients than in controls (OR, 0.51; 95% CI, 0.34-0.76; Pc, 0.0034). There was no association between HT and rs1946518. The CT haplotype was significantly more frequent in patients than in controls and conferred a risk of HT (OR, 1.76; 95% CI, 1.24-2.49; Pc, 0.0049). We concluded that the IL18 gene was associated with HT in children. The rs187238C allele and CT haplotype conferred a risk of HT.

Genetic polymorphisms in the ITPKC gene and cervical squamous cell carcinoma risk.

Cervical cancer is caused primarily by infection with oncogenic types of human papillomavirus (HPV). However, HPV infection alone is not sufficient for the progression to cervical cancer. Host immunogenetic factors may involve in the development of this disease. Inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) is recently shown to act as a negative regulator of T-cell activation. We aim to study if polymorphisms in the ITPKC gene are associated with the risk of cervical cancer in Taiwanese women. ITPKC rs28493229 C/G, rs890934 G/T, rs2303723 C/T, and rs10420685 A/G polymorphisms were genotyped in a hospital-based study of 465 women with cervical squamous cell carcinoma (CSCC) and 800 age-matched healthy control women. The presence and genotypes of HPV in CSCC were determined. The frequency of G/G genotype and G allele of the ITPKC rs28493229 polymorphism was significantly higher in patients with CSCC compared with controls (OR = 1.81, 95 % CI 1.20-2.73, P = 0.005, P (c) = 0.02; OR = 1.70, 95 % CI 1.14-2.54, P = 0.008, P (c) = 0.03, respectively). No significant associations were found for other 3 polymorphisms. Haplotype analysis revealed the distribution of haplotype CGTA was significantly reduced in women with CSCC (OR = 0.59, 95 % CI 0.40-0.89, P = 0.01, P (c) = 0.04). In conclusion, we found the G/G genotype and G allele of the ITPKC rs28493229 polymorphism may contribute to the risk of CSCC in Taiwanese women. This finding provides new insights into the mechanisms of immune activation in cervical cancer.

Genetic variability of interleukin4 gene in Taiwanese children with biliary atresia.

Biliary atresia (BA) is a neonatal cholangiopathy of unknown etiology that leads to biliary cirrhosis and is the most common cause of liver transplantation in children. A still undetermined hepatobiliary viral infection may elicit an uncontrollable autoimmune response against the biliary epithelial cells in genetically predisposed children and culminates in atresia of the biliary trees. Interleukin 4 (IL4) is crucial for the differentiation of naive T helper cells into the T helper 2 effector cells that promote humoral immunity. This study aims to investigate whether polymorphisms of the IL4 gene are associated with susceptibility to BA. Genomic DNA was extracted from whole blood samples of 53 Taiwanese children with BA and 904 ethnically-matched healthy controls. The IL4 -590 C/T, -33 C/T, and 8375 A/G polymorphisms were genotyped using the Pre-Developed TaqMan Allelic Discrimination Assay in a real-time polymerase chain reaction system. No significant difference between children with BA and healthy controls were found when comparing genotype, allele, carrier, and haplotype frequencies of these IL4 gene variants. These results suggest that the tested polymorphisms of IL4 gene are unlikely to contribute significantly to BA susceptibility in Taiwanese children.

Association of polymorphisms in the Interleukin-18 gene with susceptibility to biliary atresia.

BACKGROUND AND OBJECTIVE: Biliary atresia (BA) is a destructive inflammatory obliterative cholangiopathy of neonates that affects both intrahepatic and extrahepatic bile ducts. Although the etiology is unknown, immunologically mediated injury of the bile ducts triggered by as yet unidentified infectious agents is likely to play a critical role. Interleukin-18 (IL-18) is a proinflammatory cytokine that plays an important role in immune, infectious, and inflammatory diseases because of its induction of interferon-gamma. In this study, we investigated whether polymorphisms of the IL18 gene were associated with susceptibility to BA. PATIENTS AND METHODS: Genomic DNA was extracted from whole-blood samples of 50 Taiwanese children with BA and 1117 ethnically matched healthy controls. The IL18 -1297 T/C, -607 C/A, -137 G/C, and +105 A/C polymorphisms were genotyped using the TaqMan assay. RESULTS: No statistically significant differences of genotype, allele, carrier, and haplotype frequencies of these IL18 gene variants were found between children with BA and healthy controls. CONCLUSIONS: Our data suggest that the IL18 gene does not play a major role in BA predisposition in Taiwanese children.

Investigation of cytotoxic T-lymphocyte-associated protein 4 gene polymorphisms in symptomatic gallstone disease.

Gallstone disease (GSD), which is increasingly prevalent in Taiwan, develops through a complex process involving genetic, environmental, and immune factors. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) limits T-cell proliferation. The present study looked for associations between symptomatic GSD and polymorphisms of the CTLA4 gene. For this case-control cross-sectional study among Taiwanese, 275 patients with symptomatic GSD and 852 controls were enrolled. Genotyping of CTLA4-318 C/T, +49 A/G, and CT60 A/G single nucleotide polymorphisms (SNPs) was performed by polymerase chain reaction-restriction fragment length polymorphism. The genotype, allele, carrier, and haplotype frequencies were calculated by direct counting or with Haploview 4.1 software. Genotype, allele, carrier, and haplotype frequencies of the CTLA4 SNPs studied were equally distributed in symptomatic GSD patients and controls. No significant associations between symptomatic GSD and these 3 SNPs were observed. Our data suggest that CTLA4-318 C/T, +49 A/G, and CT60 A/G SNPs do not confer increased susceptibility to symptomatic GSD.

Genetic variation in the vascular endothelial growth factor gene is associated with biliary atresia.

BACKGROUND AND GOALS: Biliary atresia (BA) is a chronic inflammatory disease of the bile ducts resulting in biliary cirrhosis. Vascular endothelial growth factor (VEGF) has been implicated in cell-mediated inflammatory reactions. We aimed to study the relationship between genetic variations of the VEGF gene and susceptibility to BA using both case-control and family-based methodologies. STUDY: A total of 45 Taiwanese children with BA, 160 ethnically matched healthy controls, and 40 families (consisting of parents, affected children, and unaffected siblings) were studied. Three functional VEGF polymorphisms (-2578 A/C, -634 G/C, and +936 C/T) were assessed by using TaqMan assay. RESULTS: The +936 CC genotype [odds ratio (OR) 3.51, 95% confidence interval 1.54-8.01, P(c)=0.006] and C allele (OR 3.19, 95% confidence interval 1.48-6.90, P(c)=0.004) were significantly associated with increased risk of BA. The association of the +936 C allele with BA was also confirmed in a family-based association study (OR 5.7, chi2=9.8, P(c)=0.005). None of the haplotypes studied significantly influenced the risk to BA in either the case-control or family data sets. CONCLUSIONS: The VEGF +936 C/T polymorphism and particularly the C allele are associated with BA, possibly conferring increased susceptibility to the disease.

Association of interferon-gamma gene polymorphisms in Taiwanese children with biliary atresia.

BACKGROUND: Biliary atresia (BA) is a devastating neonatal hepatobiliary disease characterized by bile duct inflammation and fibrosis. The pathogenesis remains unclear, but immunologically mediated injury to bile ducts following an infectious insult is likely to play a critical role. Interferon-gamma (IFN-gamma) is a key cytokine that affects immune-mediated inflammatory responses. OBJECTIVE: This study aims to investigate whether polymorphisms of the IFN-gamma (IFNG) gene were associated with susceptibility to BA. METHODS: The IFNG -1615 C/T, -183 G/T, +874 A/T, and +2197 A/G polymorphisms were genotyped using the TaqMan assay, and CA repeat microsatellite was analyzed using capillary electrophoresis in 50 children with BA and 788 ethnically matched healthy controls. RESULTS: The distribution of genotype, allele, and haplotype frequencies of these IFNG gene variants did not differ significantly between children with BA and controls. CONCLUSION: Polymorphisms of the IFNG gene do not appear to play a major role in the genetic predisposition to BA in Taiwanese children.

Genetic polymorphisms in the CD40 ligand gene and Kawasaki disease.

BACKGROUND: Although some previous studies have reported that genetic and immunological factors play important roles in the pathogenesis of Kawasaki disease (KD), the etiological factors of this enigmatical pediatric disease are still poorly understood. PURPOSE: This study aims to investigate whether polymorphisms of the CD40 ligand (CD40L) gene are associated with KD and the development of coronary artery lesions (CAL) in the Taiwanese children. MATERIALS AND METHODS: The CD40L -3459 A/G and IVS4+121 A/G single nucleotide polymorphisms (SNPs) were genotyped in 167 children with KD and 1,010 ethnically matched healthy controls by TaqMan assay. RESULTS: None of the CD40L polymorphisms was associated with susceptibility or CAL development of KD, and this finding was supported by the haplotype analysis. CONCLUSION: In summary, these results provide little support for specific CD40L SNPs in the susceptibility or CAL development of KD in Taiwanese children. However, it will be necessary to validate or replicate this association in other independent large-size ethnic groups.

The -590 C/T and 8375 A/G interleukin-4 polymorphisms are not associated with Kawasaki disease in Taiwanese children.

Although some previous studies have reported that genetic and immunologic factors play important roles in the pathogenesis of Kawasaki disease (KD), the etiologic factors of this enigmatical pediatric disease are still poorly understood. This study aims to investigate whether polymorphisms of the interleukin-4 gene (IL-4; -590 C/T in the promoter region and 8375 A/G in intron 3) are associated with KD and the development of coronary artery lesions (CALs) in Taiwanese children. Genomic DNA was extracted from whole-blood samples from 150 children with KD and 472 ethnically matched healthy control subjects. The IL-4 -590 C/T and 8375 A/G single nucleotide polymorphisms (SNPs) were genotyped by a real-time polymerase chain reaction system with the Pre-Developed TaqMan Allelic Discrimination Assay. No significant associations between IL-4 SNPs and susceptibility of KD with CALs were found. In addition, no evidence for associations between IL-4 SNPs and CAL development was found. These results suggest that IL-4 -590 C/T and 8375 A/G SNPs do not confer a relevant role in the susceptibility or CAL development of KD in Taiwanese children.