Browsing by Author "Wan, Lei"

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Association of Interleukin-16 Polymorphisms with Graves' Disease in a Taiwanese Population
(2014-04-30)
Tsai, Kun-Hsi
;
Chang, Ching-Yao
;
Tsai, Fuu-Jen
;
Lin, Hui-Ju
;
Yang, Yuh-Shyong
Graves' disease (GD) is a complex, organ-specific autoimmune disease wherein the thyroid gland becomes enlarged and overactive. During GD progression, T cells secrete interleukin-16 (IL-16) to promote inflammation, act as chemoattractants that recruit more inflammatory cells, and activate target cells to enhance the development of GD. To investigate the role of IL-16 in GD, we genotyped 474 patients with GD at 8 single-nucleotide polymorphisms (SNPs) in the IL-16 gene. The IL-16 SNP rs8028364 was found to be associated with GD when compared with the control subjects (P = 2.93 x 10(-17); CG genotype: odds ratio [OR] = 0.2 [0.07, 0.59]; CC genotype: OR = 0.03 [0.01, 0.09]). The rs1131445 polymorphism was found to be associated with GD under the allelic model (P = 0.01; G allele: OR = 1.97 [1.17, 3.32]). Sliding-window haplotype analysis by the PLINK program showed that the most significant haplotype was provided by the 6-SNP haplotype window, consisting of rs7182786, rs8028364, rs12907134, rs4128767, rs4072111 and rs8031107 (P = 2.31 x 10(-51)). We found 2 protective haplotypes: GCAAGG (P = 8.69 x 10(-7); OR = 0.22 [0.12, 0.41]) and AGAAGG (P = 0.0012; OR = 0.26 [0.12, 0.6]). In addition, GGGGAA (P = 0.39; OR = 2.32 [1.08, 4.99]) and GGGAGA (P = 1.18 x 10(-5); OR = 5.54 [2.50, 12.31]) were found to be the two high-risk haplotypes. These results suggest that polymorphisms in IL-16 may be used as genetic markers for the diagnosis and prognosis of GD.
CRP-Cyclic AMP Regulates the Expression of Type 3 Fimbriae via Cyclic di-GMP in Klebsiella pneumoniae
(2016-09-15)
Lin, Ching-Ting
;
Lin, Tien-Huang
;
Wu, Chien-Chen
;
Wan, Lei
;
Huang, Chun-Fa
Klebsiella pneumoniae is the predominant pathogen isolated from liver abscesses of diabetic patients in Asian countries. However, the effects of elevated blood glucose levels on the virulence of this pathogen remain largely unknown. Type 3 fimbriae, encoded by the mrkABCDF genes, are important virulence factors in K. pneumoniae pathogenesis. In this study, the effects of exogenous glucose and the intracellular cyclic AMP (cAMP) signaling pathway on type 3 fimbriae expression regulation were investigated. The production of MrkA, the major subunit of type 3 fimbriae, was increased in glucose-rich medium, whereas cAMP supplementation reversed the effect. MrkA production was markedly increased by cyaA or crp deletion, but slightly decreased by cpdA deletion. In addition, the mRNA levels of mrkABCDF genes and the activity of P-mrkA were increased in Delta crp strain, as well as the mRNA levels of mrkHIJ genes that encode cyclic di-GMP (c-di-GMP)-related regulatory proteins that influence type 3 fimbriae expression. Moreover, the activities of P-mrkHI and P-mrkJ were decreased in Delta lacZ Delta crp strain. These results indicate that CRP-cAMP down-regulates mrkABCDF and mrkHIJ at the transcriptional level. Further deletion of mrkH or mrkI in Delta crp strain diminished the production of MrkA, indicating that MrkH and MrkI are required for the CRP regulation of type 3 fimbriae expression. Furthermore, the high activity of P-mrkHI in the Delta lacZ Delta crp strain was diminished in Delta lacZ Delta crp Delta mrkHI, but increased in the Delta lacZ Delta crp Delta mrkJ strain. Deletion of crp increased the intracellular c-di-GMP concentration and reduced the phosphodiesterase activity. Moreover, we found that the mRNA levels of multiple genes related to c-di-GMP metabolism were altered in Delta crp strain. These indicate that CRP regulates type 3 fimbriae expression indirectly via the c-di-GMP signaling pathway. In conclusion, we found evidence of a coordinated regulation of type 3 fimbriae expression by the CRP-cAMP and c-di-GMP signaling pathways in K. pneumoniae.
MUTYH Gene Polymorphisms as Risk Factors for Rheumatoid Arthritis
(2015-01-01)
Kung, Yung-Jen
;
Tsai, Kun Shi
;
Huang, Chung-Ming
;
Lin, Hui-Ju
;
Chen, Ter-Hsin
Objectives. MUTYH glycosylase involved in DNA repair pathways may be associated with the risk of autoimmune diseases such as rheumatoid arthritis (RA). Therefore, the association between polymorphisms in the MUTYH gene and RA was evaluated. Methods. We recruited 192 RA patients and 192 healthy subjects in Taiwan. The 4 MUTYH polymorphisms (rs3219463, rs3219476, rs3219489, and rs3219493) were detected and haplotype analysis was performed using the Bayesian method. The genotype and allelic frequency distributions of the polymorphisms in both RA patients and healthy patients were compared by the chi-square test. Results. Comparison of the genotype/allele frequencies between individuals with RA and the control groups revealed significant differences in 2 MUTYH gene polymorphisms, rs3219463 and rs3219476. After we performed a haplotype-specific analysis, the haplotypes Ht6-GTGC and Ht8-GGCG had lower presenting rates in RA patients than in the control groups. Furthermore, the genotype frequency of rs3219463 G/- was significantly increased among patients with immunoglobulin M rheumatoid factors, whereas that of rs3219476 was not. Conclusion. We demonstrated that the rs3219463 and rs3219476 polymorphisms in RA patients from a Taiwan Chinese population were associated with disease susceptibility. These data indicate that the MUTYH gene may play a role in the progression of RA.