Fuu-Jen Tsai

The aim of this study was to examine whether −627 interleukin-10 (IL-10) promoter polymorphism is a marker of susceptibility to or severity of rheumatoid arthritis (RA) in Chinese patients in Taiwan. The study included 198 Chinese patients with RA. One hundred unrelated healthy individuals living in central Taiwan served as the control subjects. The relationship between IL-10 gene polymorphism and clinical manifestations of RA was evaluated. For the genotype, allelic frequency, and carriage rate of IL-10 polymorphism, there were no statistically significant differences found between patients and controls. Furthermore, we did not detect any association of IL-10 genotype with rheumatoid factor (RF), extra-articular involvement, or bone erosion in the RA patients. The lack of association of −627 IL-10 gene polymorphism with RA and the clinical findings in our study implies that the IL-10 gene polymorphism cannot serve as a candidate gene marker for screening RA patients.

The aim of this study was to determine how polymorphisms of transporters associated with transporter and antigen processing 1 (TAP1) alleles contributed to the pathogenesis of systemic lupus erythematosus (SLE) in Taiwan. We collected 88 patients with SLE and 104 healthy people for the control group. The polymorphisms were detected as a result of polymerase chain reaction (PCR)-based restriction analysis. Associations between SLE and TAP1 polymorphisms were evaluated. The results revealed no significant differences between the healthy individuals and SLE patients with TAP1-1 (Dpn II) and TAP1-2 (Acc I) polymorphisms (P=0.10 and 0.36, respectively). However, the G alleles of TAP1-1 and TAP1-2 were significantly more common than the A alleles in serositis of SLE patients (χ²=11.16 and P=0.004, χ²=8.10 and P=0.02, respectively).

The aim of this study was to investigate the association between the polymorphism of transporters associated with antigen processing (TAP1/TAP2) genes and rheumatoid arthritis in Chinese patients. A total of 100 RA patients and 99 healthy control subjects were enrolled. Analyses with polymerase chain reaction (PCR) based restrictions were used to identify the polymorphisms of the TAP1 and TAP2 genes, which were mapped on chromosome 6. There was a significant difference in the distribution of the TAP2 gene codon 565 polymorphism frequency between the RA patients and healthy control subjects (p TAP1 gene polymorphism frequency were found between RA patients and controls. There were some physical links found between TAP1/TAP2 gene polymorphism loci. However, there was no linkage observed from TAP1/TAP2 gene polymorphisms and HLA-DRB1*04 between RA patients and healthy controls. We concluded that the TAP2 gene codon 565 ‘A’ allele was associated with RA in Chinese patients in Taiwan. Individuals possessing the ‘A’ allele had a higher incidence of RA. A lack of association of TAP1 gene polymorphisms between RA patients and healthy individuals was noted. The results of this study provide genetic evidence that TAP2 gene codon 565 polymorphism may play a role in RA.

Summary:  Purpose: The α4‐subunit gene of the neuronal nicotinic acetylcholine receptor (CHRNA4) has been identified as the first gene underlying an idiopathic partial epilepsy syndrome in human autosomal‐dominant nocturnal frontal lobe epilepsy. Studies provided evidence that the protein coded by CHRNA4 is one of the most abundant subunits of the neuronal nicotinic acetylcholine receptors in mammalian brains, and mutations of CHRNA4 seem to cause neuronal excitation. The CHRNA4 gene may have a role in the development of febrile convulsions (FCs), the majority of childhood seizures. This study assessed the distribution of genotypes of CHRNA4 in patients with FCs. Methods: A total of 102 children with FCs and 80 normal control subjects were included in the study. Polymerase chain reaction was used to identify the C/T polymorphism of the CHRNA4 gene. Genotypes and allelic frequencies for the CHRNA4 gene polymorphisms in both groups were compared. Results: The number of individuals with heterozygous CHRNA4 (Ser543Ser)‐C/T genotype was significantly greater (60.8% vs. 32.5%; p = 0.001), and the CHRNA4 (Ser543Ser)‐T allele frequency was significantly higher (p = 0.001), in patients with FCs compared with healthy controls. The odds ratio for developing FCs in individuals with the CHRNA4 (Ser543Ser)‐CT genotype was 3.77 compared with individuals with two copies of the CHRNA4 (Ser543Ser)‐C allele. Conclusions: This study demonstrated an association between the CHRNA4 gene and FCs. Individuals with the T allele had a higher incidence of FCs. These data suggest that the CHRNA4 gene or a closely linked gene might be one of the susceptibility factors for FCs.

An alternation of γ-aminobutyric acid (GABA)-ergic neurotransmission has been implicated as an etiologic factor in epileptogenesis. Missense mutations in the GABRG2 gene, which encodes the γ2 subunit of central nervous GABAA receptors, have recently been described in one family with childhood absence epilepsy and febrile seizures (FSs). FSs represent the majority of childhood seizures and have a genetic predisposition. It is not known, however, whether polymorphisms in those genes involved in familial epilepsies also contribute to the pathogenesis of FSs. By performing an association study, we used singlenucleotide polymorphisms to investigate the distribution of genotypes of GABRG2 in patients with FSs. A total of 104 children with FSs and 83 normal control subjects were included in the study. PCR was used to identify the C/T and A/G polymorphisms of the GABRG2 gene on chromosome 5q33. Genotypes and allelic frequencies for the GABRG2 gene polymorphisms in both groups were compared. The GABRG2 (nucleotide position 3145 in intron G→A) gene in both groups was not significantly different. In contrast, the number of individuals with the GABRG2 (SNP211037)-C/C genotype in patients with FSs was significantly greater compared with that in healthy control subjects (p = 0.017), and the GABRG2 (SNP211037)-C allele frequency in patients with FSs was significantly higher than that in healthy control subjects (p = 0.009). The odds ratio for developing FSs in individuals with the GABRG2 (SNP211037)-C/C genotype was 2.56 compared with individuals with the GABRG2 (SNP211037)-T/T genotype. These data suggest that the GABRG2 gene might be one of the susceptibility factors for FSs.

Growth factor-related genes regulate cell growth, differentiation and apoptosis in the kidney in response to cellular injury. One of the theories of stone formation is that cellular injury, and thus growth factors, play a role. We therefore investigated the association between growth factor genes and calcium oxalate stone disease. The most frequently seen polymorphism of the vascular endothelial growth factor (VEGF) gene is Bst U I C/T, which is located upstream at the −460th nucleotide. Other growth factor-related gene polymorphisms include the cytochrome P450c17α enzyme (CYP17) gene MspA I C/T polymorphism at the 5′-UTR promoter region, the epidermal growth factor receptor (EGFR) gene Bsr I polymorphism (A to T) at position 2,073, and the insulin-like growth factor-2 (IGF-2) gene Apa I A/G at exon 9. All four polymorphisms were used as genetic markers in this study in the search for an association between stone disease and growth factor related genes. A normal control group of 230 healthy people, and 230 patients with calcium oxalate stone, were examined. The polymorphism was seen following polymerase chain reaction based restriction analysis. The result revealed a significant difference between normal individuals and stone patients (P=0.0003, Fisher's exact test) in the distribution of the VEGF gene polymorphism as well as an odds ratio of 1.30 (95% confidence interval=0.993–1.715) per copy of the "T" allele. Whereas, the IGF-2, EGFR and CYP17 gene polymorphisms did not reveal a significant association with stone disease. We conclude that the VEGF gene Bst U I polymorphism is a suitable genetic marker of urolithiasis.

Purpose Genetic factors are known to play a role in the aetiology of glaucoma, and in particular the role of the immune system is highly suspected. In this study, we evaluated the association between tumour necrosis factor alpha -308 (TNF -308) and primary open-angle glaucoma (POAG). Methods A total of sixty POAG patients and 103 healthy volunteers as control group were enrolled in this case-controlled study. Furthermore, we used polymerase chain reaction based analysis to resolve the TNF -308 polymorphism. Statistical analysis for the relative risk of TNF -308 polymorphism was compared by the ² test. Results There were significant differences in the distribution of the polymorphism between the POAG patients and the control subjects (P=0.00016; P-308 allele occurred more frequently in POAG patients (odds ratio: 2.72; 95% confidence interval: 1.66–4.45). Conclusion The results of our study concluded that the distribution of TNF -308 was significantly higher in the POAG patients than in the control group. Therefore, the A^-308 allele appears to be associated with POAG and, therefore, could be used as a genetic marker for disease mapping. POAG is a complex disease, and a single gene could not be responsible. Understanding the role of genetic polymorphisms, like TNF , could be a prediction of the disease and useful for developing new treatments for POAG.

Congenital heart disease (CHD) is a common cardiac defect found in infants and children. Despite advances in diagnosis and treatment, our understanding of the causative mechanism and etiology of CHD is limited. To determine the genetic etiology of CHD, we selected 11 consecutive short tandem‐repeat polymorphic (STRP) markers located in the interval of the 22q11.2 region to perform genotype analysis on a large number of CHD patients (>120) and their normal relatives (>220). The results show that as regards the distribution of allelic size and frequency of these STRP markers, there were no significant differences between the CHD patients and the normal volunteers. This indicates that there is no linkage disequilibrium with these markers in CHD. In the level of heterozygosity for each marker in nonsyndromic CHD and conotruncal heart defect (CTD), there were no significant differences between the two populations. In syndromic CHD, the level of heterozygosity for D22S1648 was significantly lower than that observed in the unaffected population (χ ² = 11.25; P = 0.001). This suggests that there may be a deletion at the D22S1648 locus, and the low heterozygosity of D22S1648 indicates that this marker can be used as a genetic marker for detecting microdeletions in 22q11.2. With the use of fluorescence in situ hybridization (FISH) and real‐time quantitative polymerase chain reaction (PCR) performed on syndromic patients, we confirmed the molecular results. J. Clin. Lab. Anal. 17:28–35, 2003.