Yun Zhai

Publications (29)197.22 Total impact

• Article: A non-synonymous SNP in the NOS2 associated with septic shock in patients with sepsis in Chinese populations.

  Zhifu Wang, Kai Feng, Maoxing Yue, Xiaoguang Lu, Qihan Zheng, Hongxing Zhang, Yun Zhai, Peiyao Li, Lixia Yu, Mi Cai, [......], Weihai Shi, Xia Xia, Xi Chen, Pengbo Cao, Yuanfeng Li, Huipeng Chen, Yan Ling, Yuxia Li, Fuchu He, Gangqiao Zhou
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  ABSTRACT: Sepsis represents a systemic inflammatory response to infection and its sequelae include severe sepsis, septic shock, multiple organ dysfunction syndrome (MODS) and death. Studies in mice and humans indicate that the inducible nitric oxide synthase (iNOS, NOS2) plays an important role in the development of sepsis and its sequelae. It was reported that several single nucleotide polymorphisms (SNPs) within NOS2 could influence the production or activity of NOS2. In this study, we assessed whether SNPs within NOS2 gene were associated with severity of sepsis in Chinese populations. A case-control study was conducted, which included 299 and 280 unrelated patients with sepsis recruited from Liaoning and Jiangsu provinces in China, respectively. Six SNPs within NOS2 were genotyped using Sequenom MassARRAY system. The associations between the SNPs and risk of sepsis complications were estimated by a binary logistic regression model adjusted for confounding factors. Functional assay was performed to assess the biological significance. The GA + AA genotype of a non-synonymous SNP in the exon 16 of NOS2 (rs2297518: G>A) was significantly associated with increased susceptibility to septic shock compared with GG genotype in Liaoning population (OR = 3.29, 95 % CI = 1.40-7.72, P = 0.0047). This association was confirmed in the Jiangsu population (OR = 3.49, 95 % CI = 1.57-7.79, P = 0.0019). Furthermore, the functional assay performed in the immortalized lymphocyte cell lines indicated that the at-risk GA genotype had a tendency of higher NOS2 activity than the GG genotype (P = 0.32). Our findings suggest that the NOS2 rs2297518 may play a role in mediating the susceptibility to septic shock in patients with sepsis in Chinese populations.
  Human Genetics 11/2012; · 5.07 Impact Factor
• Source

  Available from: PubMed Central

  Article: A functional tandem-repeats polymorphism in the downstream of TERT is associated with the risk of nasopharyngeal carcinoma in Chinese population.

  Yang Zhang, Hongxing Zhang, Yun Zhai, Zhifu Wang, Fuchao Ma, Hongxue Wang, Peiyao Li, Ying Zhang, Lixia Yu, Ying Cui, Fuchu He, Gangqiao Zhou
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  ABSTRACT: Increases in human telomerase reverse transcriptase (TERT) expression and telomerase activity are frequently seen in nasopharyngeal carcinoma (NPC). Recently, a variable tandem-repeats polymorphism, MNS16A, located in the downstream region of the TERT gene, was identified and reported to have an effect on TERT expression and telomerase activity. We examined whether the functional MNS16A was related to the risk of occurrence or progression of NPC in the Chinese population. We genotyped the MNS16A polymorphism in a case-control study of 855 patients with NPC and 1036 cancer-free controls using PCR, and determined genotype by classifying the DNA band of 243 or 272 base pairs (bp) as the short (S) allele and 302 or 333 bp as the long (L) allele. The genetic associations with the risk of NPC were analyzed by logistic regression. The MNS16A genotype was not associated with the progression of NPC. However, individuals carrying the S alleles (SL + SS genotype) had a significantly reduced risk of NPC occurrence compared with those carrying the LL genotype (odds ratio (OR) = 0. 71, 95% confidence interval (CI) = 0. 52 to 0. 96, P = 0. 025). Using a immunohistochemical assay on the NPC tissues, the SL genotype carriers were found to have lower TERT expression than the LL genotype carriers (P = 0. 035). Our study indicates that the TERT MNS16A polymorphism may contribute to the risk of NPC onset in Chinese population.
  BMC Medicine 09/2011; 9:106. · 6.03 Impact Factor
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  Available from: PubMed Central

  Article: Functional polymorphism -31C/G in the promoter of BIRC5 gene and risk of nasopharyngeal carcinoma among chinese.

  Fuchao Ma, Hongxing Zhang, Yun Zhai, Wenfeng Huang, Chang Zhao, Shengqiu Ou, Hong Zhou, Wenzhao Yuan, Zhifu Wang, Hongxue Wang, Wei Yue, Lixia Yu, Peiyao Li, Xia Xia, Mi Cai, Yang Zhang, Ying Cui, Fuchu He, Yilong Ma, Gangqiao Zhou
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  ABSTRACT: Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5, also called as survivin) is a member of the inhibitor of apoptosis protein (IAP) family, which plays an important role in the occurrence and progression of cancer. Recently, a polymorphism in the promoter of BIRC5, -31C/G (rs9904341), was shown to influence BIRC5 expression. We examined whether the -31C/G was related to the risk of developing nasopharyngeal carcinoma (NPC) in a case-control population from Guangxi province in southern China, which consists of 855 patients with NPC and 1036 controls. This polymorphism was genotyped by TaqMan assay. The genetic associations with the occurrence and progression of NPC were estimated by logistic regression. We observed a statistically significant increased occurrence of NPC associated with the CC genotype (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.13-1.73; P=0.0020) compared with the genotypes containing G allele (CG + GG genotype). However, no significant association was observed for the -31C/G with the severity of NPC (as measured by tumor-node-metastasis staging system). Our findings suggest that the functional polymorphism -31C/G in the promoter of BIRC5 gene may play a role in mediating the susceptibility to NPC among Chinese.
  PLoS ONE 01/2011; 6(2):e16748. · 4.09 Impact Factor
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  Available from: Ruifu Yang

  Article: Genetic variation of the human α-2-Heremans-Schmid glycoprotein (AHSG) gene associated with the risk of SARS-CoV infection.

  Xiaohui Zhu, Yan Wang, Hongxing Zhang, Xuan Liu, Ting Chen, Ruifu Yang, Yuling Shi, Wuchun Cao, Ping Li, Qingjun Ma, Yun Zhai, Fuchu He, Gangqiao Zhou, Cheng Cao
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  ABSTRACT: Genetic background may play an important role in the process of SARS-CoV infection and SARS development. We found several proteins that could interact with the nucleocapsid protein of the SARS coronavirus (SARS-CoV). α-2-Heremans-Schmid Glycoprotein (AHSG), which is required for macrophage deactivation by endogenous cations, is associated with inflammatory regulation. Cytochrome P450 Family 3A (CYP4F3A) is an ω-oxidase that inactivates Leukotriene B4 (LTB4) in human neutrophils and the liver. We investigated the association between the polymorphisms of these two inflammation-associated genes and SARS development. The linkage disequilibrium (LD) maps of these two genes were built with Haploview using data on CHB+JPT (version 2) from the HapMap. A total of ten tag SNPs were selected and genotyped. In the Guangzhou cohort study, after adjusting for age and sex, two AHSG SNPs and one CYP4F3 SNP were found to be associated with SARS susceptibility: rs2248690 (adjusted odds ratio [AOR] 2.42; 95% confidence interval [CI] 1.30-4.51); rs4917 (AOR 1.84; 95% CI 1.02-3.34); and rs3794987 (AOR 2.01; 95% CI 1.10-3.68). To further validate the association, the ten tag SNPs were genotyped in the Beijing cohort. After adjusting for age and sex, only rs2248690 (AOR, 1.63; 95% CI, 1.30-2.04) was found to be associated with SARS susceptibility. The combined analysis of the two studies confirmed tag SNP rs2248690 in AHSG as a susceptibility variant (AOR 1.70; 95% CI 1.37-2.09). The statistical analysis of the rs2248690 genotype data among the patients and healthy controls in the HCW cohort, who were all similarly exposed to the SARS virus, also supported the findings. Further, the SNP rs2248690 affected the transcriptional activity of the AHSG promoter and thus regulated the AHSG serum level. Therefore, our study has demonstrated that the AA genotype of rs2268690, which leads to a higher AHSG serum concentration, was significantly associated with protection against SARS development.
  PLoS ONE 01/2011; 6(8):e23730. · 4.09 Impact Factor
• Article: Genome-wide association study identifies 1p36.22 as a new susceptibility locus for hepatocellular carcinoma in chronic hepatitis B virus carriers.

  Hongxing Zhang, Yun Zhai, Zhibin Hu, Chen Wu, Ji Qian, Weihua Jia, Fuchao Ma, Wenfeng Huang, Lixia Yu, Wei Yue, [......], Hao Yang, Wei Qiu, Jingmin Yang, Feng Gong, Minshan Chen, Hongbing Shen, Dongxin Lin, Yi-Xin Zeng, Fuchu He, Gangqiao Zhou
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  ABSTRACT: To identify susceptibility variants for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we conducted a genome-wide association study by genotyping 440,794 SNPs in 355 chronic HBV carriers with HCC and 360 chronic HBV carriers without HCC, all of Chinese ancestry. We identified one intronic SNP (rs17401966) in KIF1B on chromosome 1p36.22 that was highly associated with HBV-related HCC and confirmed this association in five additional independent samples, consisting of 1,962 individuals with HCC, 1,430 control subjects and 159 family trios. Across the six studies, the association with rs17401966 was highly statistically significant (joint odds ratio = 0.61, P = 1.7 x 10(-18)). In addition to KIF1B, the association region tagged two other plausible causative genes, UBE4B and PGD. Our findings provide evidence that the 1p36.22 locus confers susceptibility to HBV-related HCC, and suggest that KIF1B-, UBE4B- or PGD-related pathways might be involved in the pathogenesis of this malignancy.
  Nature Genetics 09/2010; 42(9):755-8. · 35.53 Impact Factor
• Article: Association of DLC1 gene polymorphism with susceptibility to hepatocellular carcinoma in Chinese hepatitis B virus carriers.

  Xiaoqun Dong, Gangqiao Zhou, Yun Zhai, Hongxing Zhang, Hao Yang, Lianteng Zhi, Xiumei Zhang, Jiayou Chu, Fuchu He
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  ABSTRACT: Lost or downexpression of the gene deleted in liver cancer 1 (DLC1) has been implicated in the development of hepatocellular carcinoma (HCC). We examined the relationship between DLC1 polymorphisms and HCC risk among Chinese. Three DLC1 polymorphisms, Ex11+255T>G (rs3739298), Ex11-620G>A (rs532841) and IVS19+108C>T (rs621554), were genotyped in 434 patients with HCC and 480 controls by PCR-RFLP. The associations with the susceptibility to HCC were evaluated while controlling for confounding factors. We observed significantly increased susceptibility to HCC for the C/C genotype compared with T/T of IVS19+108C>T in the HBV carriers (OR=2.95, 95% CI, 1.65-5.26, P<0.001). Compared with the haplotype G-A-T (in order of Ex11+255T>G, Ex11-620G>A and IVS19+108C>T), the haplotype T-G-C was also significantly associated with an increased susceptibility to HCC among HBV carriers (OR=2.16, 95% CI, 1.08-4.35, P=0.009). The stratified analysis indicated no modification of the confounding factors on the increased susceptibility to HCC related to the DLC1 polymorphism/haplotype. Our findings suggest that DLC1 genetic polymorphism or haplotype play a role in mediating the susceptibility to HBV-related HCC.
  Cancer epidemiology. 09/2009; 33(3-4):265-70.
• Article: Lack of association between the functional polymorphisms in the estrogen-metabolizing genes and risk for hepatocellular carcinoma.

  Xiaoyan Yuan, Gangqiao Zhou, Yun Zhai, Weimin Xie, Ying Cui, Jia Cao, Lianteng Zhi, Hongxing Zhang, Hao Yang, Xiaoai Zhang, Wei Qiu, Yong Peng, Xiumei Zhang, Ling Yu, Xia Xia, Fuchu He
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  ABSTRACT: Estrogens have been proposed to act as tumor promoters and induce hepatocarcinogenesis. Recently, we observed a significant association between the risk for hepatocellular carcinoma and the polymorphisms of the estrogen receptor (ESR) alpha (ESR1) gene, supporting the hypothesis of involvement for the estrogen-ESR axis in the estrogen-induced hepatocarcinogenesis. In this study, based on another hypothesis in which estrogen metabolites can directly cause DNA damage and affect tumor initiation, we examined whether the polymorphisms of the estrogen-metabolizing enzymes (EME), which are involved in biogenesis (CYP17, CYP19), bioavailability (CYP1A1, CYP1B1), and degradation (catechol-O-methyltransferase) of the estrogens, have any bearing on the risk for hepatocellular carcinoma. Seven functional polymorphisms in five EMEs (CYP17 MspAI site, CYP19 Trp39Arg, Ile462Val and MspI site in CYP1A1, CYP1B1 Val432Leu, and Ala72Ser and Val158Met in catechol-O-methyltransferase) were genotyped in 434 patients with hepatocellular carcinoma and 480 controls by PCR-RFLP analysis. The associations between the polymorphisms and hepatocellular carcinoma risk were evaluated while controlling for confounding factors. No significant association with the risk for hepatocellular carcinoma was observed with the seven polymorphisms in hepatitis B virus carriers and non-hepatitis B virus carriers after correction for multiple comparisons. After stratification by common confounding factors of hepatocellular carcinoma, the EME polymorphism remained no significant association with the hepatocellular carcinoma risk. Furthermore, no signs of gene-gene interactions were observed for each combination of the seven polymorphisms. Our findings suggest that the polymorphisms of EMEs may not contribute significantly to the risk for hepatocellular carcinoma.
  Cancer Epidemiology Biomarkers &amp Prevention 01/2009; 17(12):3621-7. · 4.12 Impact Factor
• Article: No association of MMP-7, MMP-8, and MMP-21 polymorphisms with the risk of hepatocellular carcinoma in a Chinese population.

  Wei Qiu, Gangqiao Zhou, Yun Zhai, Xiumei Zhang, Weimin Xie, Hongxing Zhang, Hao Yang, Lianteng Zhi, Xiaoyan Yuan, Xiaoai Zhang, Fuchu He
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  ABSTRACT: Previous studies have suggested that the functional polymorphisms in the promoters of matrix metalloproteinases (MMP) genes were associated with the risk of cancers, but no study has ever explored these polymorphisms as risk factors for hepatocellular carcinoma. Recently, we firstly examined whether seven functional polymorphisms in the promoters of MMP-1, MMP-2, MMP-3, MMP-9, MMP-12, and MMP-13 have any bearing on the risk of hepatocellular carcinoma, but we found none. In this study, we focused on an additional six MMP polymorphisms, including four functional polymorphisms in the promoters of MMP-7 (A-181G and C-153T) and MMP-8 (C-799T and A-381G), and two nonsynonymous polymorphisms in MMP-10 (A180G) and MMP-21 (C572T). With the polymorphism validation, we found that only MMP-7 A-181G, MMP-8 C-799T, and MMP-21 C572T were polymorphic. These three polymorphisms were then genotyped in 434 patients with hepatocellular carcinoma and 480 controls by PRC-RFLP analysis. The associations between the polymorphisms and hepatocellular carcinoma risk were evaluated while controlling for confounding factors. No significant association with the risk of hepatocellular carcinoma was observed with the three polymorphisms in the overall sample, hepatitis B virus carriers, and non-hepatitis B virus carriers after correction for multiple comparisons. Furthermore, when the analyses were stratified by age, sex, status of smoking and drinking, pack-years of smoking, and family history of hepatocellular carcinoma, there was also no significant association between these polymorphisms and hepatocellular carcinoma risk. Our findings suggest that the polymorphisms MMP-7 A-181G, MMP-8 C-799T, and MMP-21 C572T may not play a major role in mediating susceptibility to hepatocellular carcinoma.
  Cancer Epidemiology Biomarkers &amp Prevention 10/2008; 17(9):2514-8. · 4.12 Impact Factor
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  Available from: Zehui Yan

  Article: Regulatory polymorphisms in the promoter of CXCL10 gene and disease progression in male hepatitis B virus carriers.

  Guohong Deng, Gangqiao Zhou, Rong Zhang, Yun Zhai, Wenli Zhao, Zehui Yan, Chunqing Deng, Xiaoyan Yuan, Baoyan Xu, Xiaojia Dong, Xiumei Zhang, Xuqing Zhang, Zhijian Yao, Yan Shen, Boqing Qiang, Yuming Wang, Fuchu He
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  ABSTRACT: The importance of expression of interferon gamma-inducible protein of 10 kilodaltons (IP-10, CXCL10) during chronic hepatitis B virus (HBV) infection has been recently emphasized. In this report, we investigated whether the naturally occurred sequence variations in the CXCL10 gene impact liver damage and disease progression of chronic HBV infection. A hospital-based case-control study was conducted, and a total of 613 and 1787 unrelated Han Chinese HBV carriers were recruited from Beijing and Chongqing, respectively. We systematically screened sequence variations in the CXCL10 gene and examined the association between the variations in this gene and susceptibility to disease progression of chronic HBV infection in Chinese populations from Beijing and Chongqing. Functional analyses were conducted to verify the biological significances of the associated genetic variation. We identified that the polymorphism G-201A, located in the promoter region of CXCL10, was associated with susceptibility to disease progression in male HBV carriers (dominant model; odds ratio, 1.53; P = .001). Functional analyses show that the G-201A polymorphism alters the binding affinity of nuclear protein and regulates CXCL10 expression. We observed higher CXCL10 transcription in interferon gamma-stimulated peripheral blood mononuclear cells with the disease-susceptible genotypes. Enzyme-linked immunosorbent assay and immunohistochemical analysis showed augmented CXCL10 production in serum and liver tissues of progressed HBV carriers. The novel regulatory polymorphism G-201A [corrected] in the promoter of CXCL10 gene could be a part of the genetic variation underlying the susceptibility of individuals to disease progression of chronic HBV infection.
  Gastroenterology 04/2008; 134(3):716-26. · 11.68 Impact Factor
• Article: Functional polymorphisms and haplotypes in the promoter of the MMP2 gene are associated with risk of nasopharyngeal carcinoma.

  Gangqiao Zhou, Yun Zhai, Ying Cui, Wei Qiu, Hao Yang, Xiumei Zhang, Xiaojia Dong, Ying He, Kaitai Yao, Hongxing Zhang, Yong Peng, Xiaoyan Yuan, Lianteng Zhi, Xiaoai Zhang, Fuchu He
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  ABSTRACT: Matrix metalloproteinases (MMPs) play important roles in cancer initiation and development. Several polymorphisms in the promoters of a number of MMP genes, which can affect the respective MMP production in an allele-specific manner, have been well characterized. We examined whether these functional polymorphisms were related to the risk of nasopharyngeal carcinoma (NPC) in Chinese populations. Eight polymorphisms in the promoter of MMP1, MMP2, MMP3, MMP7, MMP9, MMP12, and MMP13 were genotyped in two independent case-control populations; one is from Guangxi province (593 patients with NPC and 480 controls), and the other is from Guangdong province (239 patients and 286 controls). We observed significantly increased susceptibility to NPC for the MMP2 -1306CC (rs243865:C>T) (odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.30-3.10) and -735CC (rs2285053:C>T) (OR = 1.56, 95% CI = 1.17-2.09) genotype carriers compared with noncarriers in the Guangxi population. This association was confirmed in the Guangdong population (for -1306CC: OR = 2.19, 95% CI = 1.21-3.96; for -735CC: OR = 1.60, 95% CI = 1.13-2.28). The C(-1306)-C(-735) haplotype was also significantly associated with increased susceptibility to NPC in both the Guangxi (OR = 1.64, 95% CI = 1.35-1.99) and Guangdong population (OR = 1.68, 95% CI = 1.29-2.19). Furthermore, stratified analysis indicated that the increased susceptibility to NPC related to the -1306CC and -735CC genotype and the C(-1306)-C(-735) haplotype was more pronounced in heavier smokers. Our findings suggest that the genetic polymorphisms or haplotype in the MMP2 promoter may play a role in mediating the susceptibility to NPC in Chinese populations.
  Human Mutation 11/2007; 28(11):1091-7. · 5.69 Impact Factor
• Article: Lack of support for an association between CLEC4M homozygosity and protection against SARS coronavirus infection.

  Lianteng Zhi, Gangqiao Zhou, Hongxing Zhang, Yun Zhai, Hao Yang, Fang Zhang, Shixin Wang, Maoti Wei, Wuchun Cao, Fuchu He
  Nature Genetics 07/2007; 39(6):692-4; author reply 694-6. · 35.53 Impact Factor
• Article: MDM2 promoter SNP309 is associated with risk of occurrence and advanced lymph node metastasis of nasopharyngeal carcinoma in Chinese population.

  Gangqiao Zhou, Yun Zhai, Ying Cui, Xiumei Zhang, Xiaojia Dong, Hao Yang, Ying He, Kaitai Yao, Hongxing Zhang, Lianteng Zhi, Xiaoyan Yuan, Wei Qiu, Xiaoai Zhang, Yan Shen, Boqing Qiang, Fuchu He
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  ABSTRACT: Mouse double minute 2 (MDM2) is a key negative regulator of the p53 activity. Recently, a polymorphism in the MDM2 intronic promoter, SNP309, was shown to influence MDM2 expression and p53 activity. We examined whether the SNP309 was related to the risk of developing nasopharyngeal carcinoma (NPC) among Chinese populations. We genotyped the SNP309 in two independent case-control populations in southern China, one is from Guangxi province (including 593 NPC patients and 480 controls) and the other is from Guangdong province (including 239 patients and 286 controls), by PCR direct sequencing. Multivariate logistic regression analysis was used to calculate adjusted odds ratio (OR) and 95% confidence interval (95% CI). We observed that compared with the TT genotype, the genotypes containing G allele (GT + GG genotype) were associated with significant increased susceptibility to NPC in both Guangxi (OR, 1.43; 95% CI, 1.04-1.91) and Guangdong population (OR, 1.53; 95% CI, 1.00-2.36). When these two sample sets were combined, the OR of the GT + GG genotype developing NPC was 1.45 (95% CI, 1.12-1.85) compared with the TT genotype. Furthermore, compared with the TT genotype, the GT + GG genotype was also significantly associated with the advanced lymph node metastasis (OR, 1.84; 95% CI, 1.09-3.05). Our findings suggest that the MDM2 SNP309 may be a risk factor for the occurrence and advanced neck lymph node metastasis of NPC in Chinese population.
  Clinical Cancer Research 06/2007; 13(9):2627-33. · 7.74 Impact Factor
• Article: Functional polymorphisms in the promoters of MMP-1, MMP-2, MMP-3, MMP-9, MMP-12 and MMP-13 are not associated with hepatocellular carcinoma risk.

  Yun Zhai, Wei Qiu, Xiao-Jia Dong, Xiu-Mei Zhang, Wei-Min Xie, Hong-Xing Zhang, Xiao-Yan Yuan, Gang-Qiao Zhou, Fu-Chu He
  Gut 04/2007; 56(3):445-7. · 10.11 Impact Factor
• Article: The association of RANTES polymorphism with severe acute respiratory syndrome in Hong Kong and Beijing Chinese

  Man Ng, Gangqiao Zhou, Wai Chong, Loretta Lee, Helen Law, Hongxing Zhang, Wilfred Wong, Susanna Fok, Yun Zhai, Raymond Yung, Eudora Chow, Ka Au, Eric Chan, Wilina Lim, Peiris JS Malik, Fuchu He, Yu Lau
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  ABSTRACT: Abstract Background Chemokines play important roles in inflammation and antiviral action. We examined whether polymorphisms of RANTES, IP-10 and Mig affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS). Methods We tested the polymorphisms of RANTES, IP-10 and Mig for their associations with SARS in 495 Hong Kong Chinese SARS patients and 578 controls. Then we tried to confirm the results in 356 Beijing Chinese SARS patients and 367 controls. Results RANTES -28 G allele was associated with SARS susceptibility in Hong Kong Chinese ( P < 0.0001, OR = 2.80, 95%CI:2.11–3.71). Individuals with RANTES -28 CG and GG genotypes had a 3.28-fold (95%CI:2.32–4.64) and 3.06-fold (95%CI:1.47–6.39) increased risk of developing SARS respectively ( P < 0.0001). This -28 G allele conferred risk of death in a gene-dosage dependent manner ( P = 0.014) with CG and GG individuals having a 2.12-fold (95% CI: 1.11–4.06) and 4.01-fold (95% CI: 1.30–12.4) increased risk. For the replication of RANTES data in Beijing Chinese, the -28 G allele was not associated with susceptibility to SARS. However, -28 CG (OR = 4.27, 95%CI:1.64–11.1) and GG (OR = 3.34, 95%CI:0.37–30.7) were associated with admission to intensive care units or death due to SARS ( P = 0.011). Conclusion RANTES -28 G allele plays a role in the pathogenesis of SARS.
  BMC Infectious Diseases. 01/2007;
• Source

  Available from: Wilfred H S Wong

  Article: The association of RANTES polymorphism with severe acute respiratory syndrome in Hong Kong and Beijing Chinese.

  Man Wai Ng, Gangqiao Zhou, Wai Po Chong, Loretta Wing Yan Lee, Helen Ka Wai Law, Hongxing Zhang, Wilfred Hing Sang Wong, Susanna Fung Shan Fok, Yun Zhai, Raymond W H Yung, Eudora Y Chow, Ka Leung Au, Eric Y T Chan, Wilina Lim, J S Malik Peiris, Fuchu He, Yu Lung Lau
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  ABSTRACT: Chemokines play important roles in inflammation and antiviral action. We examined whether polymorphisms of RANTES, IP-10 and Mig affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS). We tested the polymorphisms of RANTES, IP-10 and Mig for their associations with SARS in 495 Hong Kong Chinese SARS patients and 578 controls. Then we tried to confirm the results in 356 Beijing Chinese SARS patients and 367 controls. RANTES -28 G allele was associated with SARS susceptibility in Hong Kong Chinese (P < 0.0001, OR = 2.80, 95%CI:2.11-3.71). Individuals with RANTES -28 CG and GG genotypes had a 3.28-fold (95%CI:2.32-4.64) and 3.06-fold (95%CI:1.47-6.39) increased risk of developing SARS respectively (P < 0.0001). This -28 G allele conferred risk of death in a gene-dosage dependent manner (P = 0.014) with CG and GG individuals having a 2.12-fold (95% CI: 1.11-4.06) and 4.01-fold (95% CI: 1.30-12.4) increased risk. For the replication of RANTES data in Beijing Chinese, the -28 G allele was not associated with susceptibility to SARS. However, -28 CG (OR = 4.27, 95%CI:1.64-11.1) and GG (OR = 3.34, 95%CI:0.37-30.7) were associated with admission to intensive care units or death due to SARS (P = 0.011). RANTES -28 G allele plays a role in the pathogenesis of SARS.
  BMC Infectious Diseases 01/2007; 7:50. · 3.12 Impact Factor
• Article: Estrogen receptor alpha polymorphisms associated with susceptibility to hepatocellular carcinoma in hepatitis B virus carriers.

  Yun Zhai, Gangqiao Zhou, Guohong Deng, Weimin Xie, Xiaojia Dong, Xiumei Zhang, Ling Yu, Hao Yang, Xiaoyan Yuan, Hongxin Zhang, Lianteng Zhi, Zhijian Yao, Yan Shen, Boqing Qiang, Fuchu He
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  ABSTRACT: Overexpression of estrogen receptors (ESRs) is implicated in the development of hepatocellular carcinoma (HCC) in both animal models and humans. We examined whether the ESR1 polymorphisms were related to HCC risk among chronic hepatitis B virus carriers. Six ESR1 polymorphisms, which are (TA)n repeat in the promoter, T29C at codon 10 in exon 1, PvuII and XbaI site in intron 1, C136474G at codon 325 in exon 4, and A252966G in intron 5, were genotyped in 248 patients with HCC and 239 controls. The associations with the susceptibility to HCC were estimated by logistic regression. Allele-specific transcription difference of ESR1 messenger RNA was performed by real-time quantitative polymerase chain reaction. We observed a statistically significant increased susceptibility to HCC associated with the homozygous alleles with a high number of TA repeats (assigned as H/H genotype; odds ratio [OR], 2.66; 95% confidence interval [CI], 1.44-4.94; P = .0018), T29C C/C genotype (OR, 2.31; 95% CI, 1.25-4.26; P = .0076), and PvuII C/C genotype (OR, 2.19; 95% CI, 1.27-3.78; P = .0048) compared with the homozygous alleles with a low number of TA repeats (assigned as L/L genotype), T29C T/T, and PvuII T/T genotype, respectively. In accordance, the relative messenger RNA levels of the at-risk C allele of T29C were consistently higher than those of the T allele in heterozygous cells. Our findings suggest that the genetic polymorphism in ESR1 may play a role in mediating susceptibility to HCC in Chinese hepatitis B virus carriers.
  Gastroenterology 07/2006; 130(7):2001-9. · 11.68 Impact Factor
• Article: Association between mannose-binding lectin gene polymorphisms and susceptibility to severe acute respiratory syndrome coronavirus infection.

  Hongxing Zhang, Gangqiao Zhou, Lianteng Zhi, Hao Yang, Yun Zhai, Xiaojia Dong, Xiumei Zhang, Xue Gao, Yunping Zhu, Fuchu He
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  ABSTRACT: Genetic determinants of susceptibility to severe acute respiratory syndrome coronavirus (SARS-CoV) infection remain unknown. We assessed whether mannose-binding lectin (MBL) gene polymorphisms were associated with susceptibility to SARS-CoV infection or disease severity in an ethnically homogeneous population born in northern China. The frequencies of 1 mutation in codon 54 and 3 promoter polymorphisms at nt -550, -221, and 4 were ascertained in 352 patients with SARS and 392 control subjects, by means of polymerase chain reaction direct sequencing. Of 352 patients with SARS and 392 control subjects, 120 (34.4%) and 91 (23.2%) were carriers of the codon 54 variant, respectively (odds ratio [OR], 1.73 [95% confidence interval {CI}, 1.25-2.39]; P=.00086). A total of 123 (36.0%) of 352 patients with SARS and 100 (25.5%) of 392 control subjects had haplotype pairs associated with medium or low expression of MBL (OR, 1.67 [95% CI, 1.21-2.29]; P=.00187). The population-attributable fraction of patients with SARS that was associated with having the codon 54 variant was 20.1% (95% CI, 7.9%-32.3%). MBL gene polymorphisms were significantly associated with susceptibility to SARS-CoV infection; this might be explained by the reduced expression of functional MBL secondary to having the codon 54 variant.
  The Journal of Infectious Diseases 11/2005; 192(8):1355-61. · 6.41 Impact Factor
• Article: [Study on single nucleotide polymorphism of TLR4 in Chinese population].

  Kai Feng, Gang-qiao Zhou, Yun Zhai, Pei-fang Zhu, Zheng-guo Wang, Fu-chu He, Jian-xin Jiang
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  ABSTRACT: To identify the single nucleotide polymorphisms(SNPs) in the regulatory and coding regions of human Toll-like receptor 4(TLR4) gene and to search for its new genetic makers. The 5' flank region, exons, parts of the introns, as well as 3' flank region of TLR4 gene were sequenced to identify and characterize the SNPs in Chinese population. SNP genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism for 2 highly distributed SNPs. Five novel SNPs were identified through a 4.98 kb sequencing of TLR4 gene. Among them, three were in 5'flank region, two in 3'UTR. In the sample of Han population from Chongqing, the minor allele frequencies of two highly distributed SNPs were 0.266 and 0.404 respectively. Sampling analysis in Han population of Chongqing showed that the two highly distributed SNPs of TLR4 were common in Chinese population and could be used for genetic marker of TLR4 gene.
  Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 03/2005; 22(1):99-101.
• Article: [An investigation of polymorphism in IL-1R1 gene in Chinese population and the functional prediction of a variation in the transmembrane region of IL-1R1].

  Kai Feng, Gang-qiao Zhou, Yun Zhai, Pei-fang Zhu, Zheng-guo Wang, Fu-chu He, Jian-xin Jiang
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  ABSTRACT: To identify the single nucleotide polymorphisms (SNPs) in the regulatory and coding regions of human interleukin-1 receptor type I (IL-1R1) gene and to assess their potential effect on the function of IL-1R1. The 5' flank region, exons, parts of the introns, as well as 3' flank region of IL-1R1 gene were sequenced to identify and characterize the SNPs in Chinese population. Effects of the SNP on the structure and function of IL-1R1 were analyzed by computational methods. Sixteen SNPs were identified through a 9643 bp sequencing of IL-1R1 gene. Among them, four were in 5' flank region, four in intron region, one in coding region, and seven in 3' untranslated region. A novel SNP in Chinese population was involved in a structural change in IL-1R1, which may influence the signal transduction of IL-1R1. The SNP in the IL-1R1 gene might influence its function as an important receptor of IL-1 family.
  Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 09/2004; 21(4):316-20.
• Article: Hepatopoietin interacts directly with COP9 signalosome and regulates AP-1 activity.

  Yan Wang, Chengrong Lu, Handong Wei, Na Wang, Xiaoxiao Chen, Lingqiang Zhang, Yun Zhai, Yunping Zhu, Yinglin Lu, Fuchu He
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  ABSTRACT: Hepatopoietin (HPO)/augmenter of liver regeneration (ALR) is a specific hepatotrophic growth factor, which plays a key role in liver regeneration. Our previous study indicated that HPO executes its function by an inter-reactive network of the autocrine, paracrine and endocrine pathways. Recently, we have demonstrated that intracellular HPO interacts with Jun activation domain-binding protein 1 (JAB1) and leads to potentiation of activating protein-1 (AP-1) activity in a MAPK independent fashion. JAB1 is the fifth subunit of the COP9 signalosome (CSN), which is first identified as a suppressor of plant morphogenesis. A protein complex kinase activity associated with the CSN has been reported but not identified yet. In this report, we investigated further the association of HPO with the whole CSN. HPO exists in a complex with the eight-component CSN, both when purified from glycerol gradient centrifugation and when reciprocal immunoprecipitated from the lysates of transfected COS-7 cells. Intracellular HPO colocalizes with endogenous CSN in nucleus of hepatic cells. In addition, intracellular function of HPO that increases the phosphorylation of c-Jun leading to potentiate the AP-1 activity is inhibited by curcumin, a potent inhibitor of CSN-associated kinase. Taken together, these results elucidate a novel relationship of intracellular growth factor, HPO with large protein complex, CSN, which suggests a possible linkage between CSN and liver regeneration.
  FEBS Letters 09/2004; 572(1-3):85-91. · 3.54 Impact Factor