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Liu H.,Shandong University | Liu H.,Shandong Academy of Sciences | Liu H.,Shandong Provincial Key Laboratory for Dermatovenereology | Irwanto A.,Agency for Science, Technology and Research Singapore | And 55 more authors.
Nature Genetics | Year: 2015

Genome-wide association studies (GWAS) have led to the discovery of several susceptibility loci for leprosy with robust evidence, providing biological insight into the role of host genetic factors in mycobacterial infection. However, the identified loci only partially explain disease heritability, and additional genetic risk factors remain to be discovered. We performed a 3-stage GWAS of leprosy in the Chinese population using 8,313 cases and 16,017 controls. Besides confirming all previously published loci, we discovered six new susceptibility loci, and further gene prioritization analysis of these loci implicated BATF3, CCDC88B and CIITA-SOCS1 as new susceptibility genes for leprosy. A systematic evaluation of pleiotropic effects demonstrated a high tendency for leprosy susceptibility loci to show association with autoimmunity and inflammatory diseases. Further analysis suggests that molecular sensing of infection might have a similar pathogenic role across these diseases, whereas immune responses have discordant roles in infectious and inflammatory diseases. © 2015 Nature America, Inc. All rights reserved. Source


Liu H.,Shandong Academy of Sciences | Liu H.,Shandong University | Liu H.,Shandong Provincial Key Laboratory for Dermatovenereology | Liu H.,Shandong Provincial Medical Center for Dermatovenereology | And 61 more authors.
American Journal of Human Genetics | Year: 2012

Of eight leprosy susceptibility loci identified by genome-wide association studies, five have been implicated in Crohn disease, suggesting a common genetic fingerprint between leprosy and inflammatory bowel disease (IBD). Here, we conducted a multiple-stage genetic association study of 133 IBD susceptibility loci in multiple leprosy samples (totaling 4,971 leprosy cases and 5,503 controls) from a Chinese population and discovered two associations at rs2058660 on 2q12.1 (p = 4.57 × 10-19; odds ratio [OR] = 1.30) and rs6871626 on 5q33.3 (p = 3.95 × 10-18; OR = 0.75), implicating IL18RAP/IL18R1 and IL12B as susceptibility genes for leprosy. Our study reveals the important role of IL12/IL18-mediated transcriptional regulation of IFN-γ production in leprosy, and together with previous findings, it demonstrates the shared genetic susceptibility between infectious and inflammatory diseases. © 2012 The American Society of Human Genetics. Source


Jin P.,Shandong University | Jin P.,National University of Singapore | Andiappan A.K.,Agency for Science, Technology and Research Singapore | Andiappan A.K.,National University of Singapore | And 30 more authors.
Journal of Allergy and Clinical Immunology | Year: 2015

Background Brain-derived neurotrophic factor (BDNF) is a secretory protein that has been implicated in the pathogenesis of allergic rhinitis (AR), atopic asthma, and eczema, but it is currently unknown whether BDNF polymorphisms influence susceptibility to moderate-to-severe AR. Objective We sought to identify disease associations and the functional effect of BDNF genetic variants in patients with moderate-to-severe AR. Methods Tagging single nucleotide polymorphisms (SNPs) spanning the BDNF gene were selected from the human HapMap Han Chinese from Beijing (CHB) data set, and associations with moderate-to-severe AR were assessed in 2 independent cohorts of Chinese patients (2216 from Shandong province and 1239 living in Singapore). The functional effects of the BDNF genetic variants were determined by using both in vitro and ex vivo assays. Results The tagging SNP rs10767664 was significantly associated with the risk of moderate-to-severe AR in both Singapore Chinese (P =.0017; odds ratio, 1.324) and Shandong Chinese populations (P =.039; odds ratio, 1.180). The coding nonsynonymous SNP rs6265 was in perfect linkage with rs10767664 and conferred increased BDNF protein secretion by a human cell line in vitro. Subjects bearing the AA genotype of rs10767664 exhibited increased risk of moderate-to-severe AR and displayed increased BDNF protein and total IgE levels in plasma. Using a large-scale expression quantitative trait locus study, we demonstrated that BDNF SNPs are significantly associated with altered BDNF concentrations in peripheral blood. Conclusion A common genetic variant of the BDNF gene is associated with increased risk of moderate-to-severe AR, and the AA genotype is associated with increased BDNF mRNA levels in peripheral blood. Together, these data indicate that functional BDNF gene variants increase the risk of moderate-to-severe AR. © 2015 American Academy of Allergy, Asthma & Immunology. Source


Yang B.,Shandong Academy of Sciences | Yang B.,Shandong Provincial Key Laboratory for Dermatovenereology | Wang C.,Shandong Academy of Sciences | Wang C.,Shandong Provincial Key Laboratory for Dermatovenereology | And 13 more authors.
Pediatric Dermatology | Year: 2012

Epidermolysis bullosa acquisita (EBA) is a rare, acquired, subepidermal blistering disease characterized by autoantibodies directed against type VII collagen, the major component of anchoring fibrils. We report a 5-year-old Chinese boy who presented with extensive lesions consisting of disseminated pruritic vesicles and tense blisters. The diagnosis of EBA was confirmed by histopathology, immunofluorescence, and immunoblotting analysis. The disease was controlled with a combination of prednisone and dapsone. © 2012 Wiley Periodicals, Inc. Source


Sun Y.,Shandong Academy of Sciences | Sun Y.,Shandong Provincial Key Laboratory for Dermatovenereology | Liu H.,Shandong Academy of Sciences | Liu H.,Shandong Provincial Key Laboratory for Dermatovenereology | And 11 more authors.
Experimental Dermatology | Year: 2011

Leprosy is caused by Mycobacterium leprae, and the global registered prevalence of leprosy at the beginning of 2009 stood at 213036 cases. It has long been thought that leprosy has a strong genetic risk. Recently, we have identified significant associations (P<1.00×10-10) between SNPs in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR and RIPK2 and a trend towards an association (P=5.10×10-5) with a SNP in LRRK2. Here, we investigated the expression of these seven genes in formalin-fixed, paraffin-embedded skin tissues of leprosy and matched normal tissues using branched DNA technology. This technology allows for direct measurement of targeted mRNA within cellular lysate using a 96-well plate format in a time frame compared to a reporter gene assay. The clear upregulation of all seven genes was found in leprosy tissues compared to normal tissues, which further supports our genome-wide association study results. © 2011 John Wiley & Sons A/S. Source

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