Xuejun Zhang
Anhui Medical University
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Xuejun Zhang.
The New England Journal of Medicine | 2009
Furen Zhang; Wei Huang; Shumin Chen; Liangdan Sun; Liu H; Yi Li; Yong Cui; Xiaoxiao Yan; Haitao Yang; Rong-De Yang; Tongsheng Chu; Chi Zhang; Lin Zhang; Jian-Wen Han; Gongqi Yu; Cheng Quan; Yongxiang Yu; Zheng Zhang; Benqing Shi; Lian-Hua Zhang; Hui Cheng; Changyuan Wang; Yan Lin; Hou-Feng Zheng; Xi-An Fu; Xianbo Zuo; Qiang Wang; Heng Long; Yi-Ping Sun; Yi-Lin Cheng
BACKGROUND The narrow host range of Mycobacterium leprae and the fact that it is refractory to growth in culture has limited research on and the biologic understanding of leprosy. Host genetic factors are thought to influence susceptibility to infection as well as disease progression. METHODS We performed a two-stage genomewide association study by genotyping 706 patients and 1225 controls using the Human610-Quad BeadChip (Illumina). We then tested three independent replication sets for an association between the presence of leprosy and 93 single-nucleotide polymorphisms (SNPs) that were most strongly associated with the disease in the genomewide association study. Together, these replication sets comprised 3254 patients and 5955 controls. We also carried out tests of heterogeneity of the associations (or lack thereof) between these 93 SNPs and disease, stratified according to clinical subtype (multibacillary vs. paucibacillary). RESULTS We observed a significant association (P<1.00x10(-10)) between SNPs in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association (P=5.10x10(-5)) with a SNP in LRRK2. The associations between the SNPs in C13orf31, LRRK2, NOD2, and RIPK2 and multibacillary leprosy were stronger than the associations between these SNPs and paucibacillary leprosy. CONCLUSIONS Variants of genes in the NOD2-mediated signaling pathway (which regulates the innate immune response) are associated with susceptibility to infection with M. leprae.
Nature Genetics | 2010
Cheng Quan; Yunqing Ren; Lei-Hong Xiang; Liangdan Sun; Ai-E Xu; Xing-Hua Gao; Hong-Duo Chen; Xiong-Ming Pu; Ri-Na Wu; Chao-Zhao Liang; Jia-Bin Li; Tianwen Gao; Jianzhong Zhang; Xiu-Li Wang; Jun Wang; Rong-Ya Yang; Ling Liang; Jian-Bin Yu; Xianbo Zuo; Sheng-Quan Zhang; Shu-Mei Zhang; Gang Chen; Pan Li; Jun Zhu; Yong-Wei Li; Xiao-Dong Wei; Wei-Song Hong; Ying Ye; Yong Zhang; Wei-Su Wu
We conducted a genome-wide association study of generalized vitiligo in the Chinese Han population by genotyping 1,117 cases and 1,429 controls. The 34 most promising SNPs were carried forward for replication in samples from individuals of the Chinese Han (5,910 cases and 9,916 controls) and Chinese Uygur (713 cases and 824 controls) populations. We identified two independent association signals within the major histocompatibility complex (MHC) region (rs11966200, Pcombined = 1.48 × 10−48, OR = 1.90; rs9468925, Pcombined = 2.21 × 10−33, OR = 0.74). Further analyses suggested that the strong association at rs11966200 might reflect the reported association of the HLA-A*3001, HLA-B*1302, HLA-C*0602 and HLA-DRB1*0701 alleles and that the association at rs9468925 might represent a previously unknown HLA susceptibility allele. We also identified one previously undescribed risk locus at 6q27 (rs2236313, Pcombined = 9.72 × 10−17, OR = 1.20), which contains three genes: RNASET2, FGFR1OP and CCR6. Our study provides new insights into the genetic basis of vitiligo.
Journal of Autoimmunity | 2013
Yong Cui; Yujun Sheng; Xuejun Zhang
Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic component, characterized by hyperactive T and B cells, autoantibody production, immune complex deposition and multi-organ damage. It affects predominantly women of child-bearing age and has population differences in both disease prevalence and severity. Genetic factors are known to play key roles in the disease through the use of association and family studies. Previously, SLE susceptibility genes were mainly revealed through linkage analysis and candidate gene studies. Since 2008, our understanding of the genetic basis of SLE has been rapidly advanced through genome-wide association studies (GWASs). More than 40 robust susceptibility loci have been identified and conformed to be associated with SLE using this technique. Most of these associated genes productions participate in important pathways involved in the pathogenesis of SLE, such as immune complex processing, toll-like receptor signaling, type I interferon production, and so on. A number of susceptibility loci with unknown functions in the pathogenesis of SLE have also been identified, indicating that additional molecular mechanisms contribute to the risk of developing SLE. It is noteworthy that susceptibility loci of SLE are shared by other immune-related diseases. Thus, common molecular pathways may be involved in the pathogenesis of these diseases. In this review, we summarize the key loci, achieving genome-wide significance, which have been shown to predispose to SLE. Analysis of relevant molecular pathways suggests new etiologic clues to SLE development. These genetic loci may help building the foundation for genetic diagnosis and personalized treatment for patients with SLE in the near future. However, substantial additional studies, including functional and gene-targeted studies, are required to confirm the causality of the genetic variants and their biological relevance in SLE development.
Nature Genetics | 2012
Jianfeng Xu; Zengnan Mo; Dingwei Ye; Meilin Wang; Fang Liu; Guangfu Jin; Chuanliang Xu; Xiang Wang; Qiang Shao; Zhiwen Chen; Zhihua Tao; Jun Qi; Fangjian Zhou; Zhong Wang; Yaowen Fu; Dalin He; Qiang Wei; Jianming Guo; Denglong Wu; Xin Gao; Jianlin Yuan; Gongxian Wang; Yong Xu; Guozeng Wang; Haijun Yao; Pei Dong; Yang Jiao; Mo Shen; Jin Yang; Jun OuYang
Prostate cancer risk–associated variants have been reported in populations of European descent, African-Americans and Japanese using genome-wide association studies (GWAS). To systematically investigate prostate cancer risk–associated variants in Chinese men, we performed the first GWAS in Han Chinese. In addition to confirming several associations reported in other ancestry groups, this study identified two new risk-associated loci for prostate cancer on chromosomes 9q31.2 (rs817826, P = 5.45 × 10−14) and 19q13.4 (rs103294, P = 5.34 × 10−16) in 4,484 prostate cancer cases and 8,934 controls. The rs103294 marker at 19q13.4 is in strong linkage equilibrium with a 6.7-kb germline deletion that removes the first six of seven exons in LILRA3, a gene regulating inflammatory response, and was significantly associated with the mRNA expression of LILRA3 in T cells (P < 1 × 10−4). These findings may advance the understanding of genetic susceptibility to prostate cancer.
Nature Genetics | 2014
Huayang Tang; Xin Jin; Yang Li; Hui Jiang; Xianfa Tang; Xu Yang; Hui Cheng; Ying Qiu; Gang Chen; Junpu Mei; Fusheng Zhou; Renhua Wu; Xianbo Zuo; Yong Zhang; Qi Cai; Xianyong Yin; Cheng Quan; Haojing Shao; Yong Cui; Fangzhen Tian; Xia Zhao; Liu H; Feng-Li Xiao; Fengping Xu; Jian-Wen Han; Dongmei Shi; Anping Zhang; Cheng Zhou; Qibin Li; Xing Fan
To explore the contribution of functional coding variants to psoriasis, we analyzed nonsynonymous single-nucleotide variants (SNVs) across the genome by exome sequencing in 781 psoriasis cases and 676 controls and through follow-up validation in 1,326 candidate genes by targeted sequencing in 9,946 psoriasis cases and 9,906 controls from the Chinese population. We discovered two independent missense SNVs in IL23R and GJB2 of low frequency and five common missense SNVs in LCE3D, ERAP1, CARD14 and ZNF816A associated with psoriasis at genome-wide significance. Rare missense SNVs in FUT2 and TARBP1 were also observed with suggestive evidence of association. Single-variant and gene-based association analyses of nonsynonymous SNVs did not identify newly associated genes for psoriasis in the regions subjected to targeted resequencing. This suggests that coding variants in the 1,326 targeted genes contribute only a limited fraction of the overall genetic risk for psoriasis.
Nature Genetics | 2013
David Ellinghaus; Hansjörg Baurecht; Elke Rodriguez; Anja Matanovic; Ingo Marenholz; Norbert Hubner; Heidi Schaarschmidt; Natalija Novak; Sven Michel; Laura Maintz; Thomas Werfel; Ulf Meyer-Hoffert; Melanie Hotze; Holger Prokisch; Katharina Heim; Christian Herder; Tomomitsu Hirota; Mayumi Tamari; Michiaki Kubo; Atsushi Takahashi; Yusuke Nakamura; Lam C. Tsoi; Philip E. Stuart; James T. Elder; Liangdan Sun; Xianbo Zuo; Sen Yang; Xuejun Zhang; Per Hoffmann; Markus M. Nöthen
Atopic dermatitis is a common inflammatory skin disease with a strong heritable component. Pathogenetic models consider keratinocyte differentiation defects and immune alterations as scaffolds, and recent data indicate a role for autoreactivity in at least a subgroup of patients. FLG (encoding filaggrin) has been identified as a major locus causing skin barrier deficiency. To better define risk variants and identify additional susceptibility loci, we densely genotyped 2,425 German individuals with atopic dermatitis (cases) and 5,449 controls using the Immunochip array followed by replication in 7,196 cases and 15,480 controls from Germany, Ireland, Japan and China. We identified four new susceptibility loci for atopic dermatitis and replicated previous associations. This brings the number of atopic dermatitis risk loci reported in individuals of European ancestry to 11. We estimate that these susceptibility loci together account for 14.4% of the heritability for atopic dermatitis.
Diabetes | 2013
Huaixing Li; Wei Gan; Ling Lu; Xiao Dong; Xueyao Han; Cheng Hu; Zhen Yang; Liang Sun; Wei Bao; Pengtao Li; Meian He; Liangdan Sun; Yiqin Wang; Jingwen Zhu; Qianqian Ning; Yong Tang; Rong Zhang; Jie Wen; Di Wang; Xilin Zhu; Kunquan Guo; Xianbo Zuo; Xiaohui Guo; Handong Yang; Xianghai Zhou; Xuejun Zhang; Lu Qi; Ruth J. F. Loos; Frank B. Hu; Tangchun Wu
Substantial progress has been made in identification of type 2 diabetes (T2D) risk loci in the past few years, but our understanding of the genetic basis of T2D in ethnically diverse populations remains limited. We performed a genome-wide association study and a replication study in Chinese Hans comprising 8,569 T2D case subjects and 8,923 control subjects in total, from which 10 single nucleotide polymorphisms were selected for further follow-up in a de novo replication sample of 3,410 T2D case and 3,412 control subjects and an in silico replication sample of 6,952 T2D case and 11,865 control subjects. Besides confirming seven established T2D loci (CDKAL1, CDKN2A/B, KCNQ1, CDC123, GLIS3, HNF1B, and DUSP9) at genome-wide significance, we identified two novel T2D loci, including G-protein–coupled receptor kinase 5 (GRK5) (rs10886471: P = 7.1 × 10−9) and RASGRP1 (rs7403531: P = 3.9 × 10−9), of which the association signal at GRK5 seems to be specific to East Asians. In nondiabetic individuals, the T2D risk-increasing allele of RASGRP1-rs7403531 was also associated with higher HbA1c and lower homeostasis model assessment of β-cell function (P = 0.03 and 0.0209, respectively), whereas the T2D risk-increasing allele of GRK5-rs10886471 was also associated with higher fasting insulin (P = 0.0169) but not with fasting glucose. Our findings not only provide new insights into the pathophysiology of T2D, but may also shed light on the ethnic differences in T2D susceptibility.
American Journal of Human Genetics | 2013
Wanling Yang; Huayang Tang; Yan Zhang; Xianfa Tang; Jing Zhang; Liangdan Sun; Jing Yang; Yong Cui; Lu Zhang; Nattiya Hirankarn; Hui Cheng; Hai-Feng Pan; Jinping Gao; Tsz Leung Lee; Yujun Sheng; Chak Sing Lau; Yang Li; Tak Mao Chan; Xianyong Yin; Dingge Ying; Qianjin Lu; Alexander Moon Ho Leung; Xianbo Zuo; Xiang Chen; Kwok Lung Tong; Fusheng Zhou; Qingchun Diao; Niko Kei Chiu Tse; Hongfu Xie; Chi Chiu Mok
Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases.
Journal of Medical Genetics | 2008
M. Sun; X. Zeng; Q. Liu; X.-L. Zhao; F.-X. Wu; G.-P. Wu; Zhenguo Zhang; B. Gu; Y.-F. Zhao; S.-H. Tian; Bin Lin; Xiangyin Kong; Xianglin Zhang; W. Yang; W. H.-Y. Lo; Xuejun Zhang
Background: The Sonic hedgehog (SHH) protein produced in the zone of polarising activity (ZPA) is a major determinant of the identity and numbers of digits in early limb development. Preaxial polydactyly types II (PPD2) and III (PPD3) have been mapped to a critical region at 7q36, and subsequently shown to be caused by point mutations in the ZPA regulatory sequence (ZRS), a long range cis-regulator for the SHH gene. Triphalangeal thumb–polysyndactyly syndrome (TPTPS) and syndactyly type IV (SD4) were also mapped to the 7q36 region but pathogenic mutations in ZRS have not yet been affirmed. Methods and results: We performed linkage and haplotype analysis in six Han Chinese families with TPTPS and/or SD4, and refined the disease locus to an interval of 646 kb containing ZRS. In all families, the affected individuals heterozygous at rs10254391 (a single nucleotide polymorphism within ZRS) revealed a remarkable allele imbalance on sequence chromatogram. Using real-time quantitative polymerase chain reaction (qPCR), we identified duplication of ZRS and found that this duplication segregated with the limb phenotypes in all families but was not detected in unaffected family members or in unrelated control individuals. The duplication was also confirmed by interphase fluorescence in situ hybridisation (FISH) in an affected individual. We designed 17 additional qPCR assays and defined the minimum duplications in all six families, ranging from 131kb to 398kb. Conclusion: Both TPTPS and SD4 are due to duplications involving ZRS, the limb specific SHH enhancer. Point mutations in the ZRS and duplications encompassing the ZRS cause distinctive limb phenotypes.
Acta Dermato-venereologica | 2007
Xing Fan; Sen Yang; Liang Dan Sun; Yan Hua Liang; Min Gao; Kai Yue Zhang; Wei Huang; Xuejun Zhang
HLA-Cw6 is strongly associated with psoriasis and has been suggested to be the PSORS1 gene that confers susceptibility to early-onset psoriasis. In this study of the clinical features of HLA-Cw*0602-positive and -negative psoriasis patients in a Han Chinese population, we typed HLA-C in a cohort of 679 patients and compared the two groups. Cw*0602-positive patients (n=345) had an earlier disease onset (p < 1 x 10(-5)), more severe disease (p < 1 x 10(-3)), higher frequency of guttate psoriasis (p < 1 x 10(-9)), more affected legs and trunk (p < 1 x 10(-5)), higher incidence of Köbners phenomenon (p=0.005) and of trauma history (p=0.009). Cw*0602-negative patients (n= 334) had more palmoplantar pustulosis (p=0.004), nail changes (p=0.001) and scalp involvement (p=0.007). However, there was no statistically significant difference between the two groups regarding age, gender, incidence of plaque psoriasis, erythrodermic, inverse, psoriatic arthritis, and the precipitation factors stress and infection. The study showed that Cw*0602-positive patients had some obvious clinical differences from Cw*0602-negative patients in a Han Chinese population, which provides evidence for an HLA-Cw*0602-associated phenotype in psoriasis.