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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.


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.


Luo B.F.,U.S. Center for Disease Control and Prevention | Du L.,U.S. Center for Disease Control and Prevention | Li J.X.,Peking University | Pan B.Y.,U.S. Center for Disease Control and Prevention | And 8 more authors.
Journal of Medical Genetics | Year: 2010

Objective: To estimate heritability of metabolic syndrome traits among healthy younger adults in a human population in China, and examine potential sex differences in heritability and parental effect on metabolic syndrome traits. Methods: Using offspring - parent regression, we estimated heritability (h 2) of metabolic syndrome traits based on 452 child-parent triads identified from a population based random survey on metabolic syndrome among people over 15 years of age in Guangzhou, China. Results: Body mass index (BMI), cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG) and waist circumference (waist-C) were more heritable (h2, 0.42-0.545), whereas systolic blood pressure (SBP), diastolic blood pressure (DBP), and triglycerides (TG) were less heritable (h2, 0.14-0.28). Sons had pronounced increases in heritability for all traits over daughters, particularly for cholesterol (0.653 vs 0.356), FPG (0.602 vs 0.313), LDL-C (0.521 vs 0.329), and TG (0.395 vs 0.187). Offspringemother seemed to have a higher heritability in every trait except FPG (0.67 vs 0.794) than offspring - father, most notably for DBP (0.308 vs 0.122), SBP (0.288 vs 0.146), TG (0.387 vs 0.239) and waist-C (0.581 vs 0.354). Conclusion: We estimated the heritability of metabolic syndrome traits in a human population based on a unique population based offspring - parent sample from China, and found important evidence that the maternal and paternal effects on these traits are different and the sex difference in heritability is pronounced.


Ni D.,Anhui Medical University | Ni D.,Key Laboratory of Gene Resource Utilization for Severe Diseases | Yu H.,Anhui Medical University | Yu H.,Key Laboratory of Gene Resource Utilization for Severe Diseases | And 9 more authors.
BioMed Research International | Year: 2013

We investigated the effect of murine cytomegalovirus (MCMV) on interstitial pneumonia in transplant recipients in an experimental skin allograft model. Skin transplantation between C57BL/6J and BALB/c mice was performed in the presence or absence of cyclosporin A treatment. Flow cytometry showed that the number of CD4+ and CD8+ cells and the level of IFN-γ decreased significantly in the groups treated with cyclosporin A. We either mock-infected or infected the mice with MCMV by intranasal administration and monitored pathophysiological behavior and body weight. The infected mice were sacrificed at different days postinfection for histology, immunohistochemistry, and molecular biological evaluations. Interstitial pneumonitis was observed in positive control groups as well as in experimental group that received cyclosporin A, a skin transplant, and infected with the highest dose of virus (105 PFU). Transmission electronic microscopy demonstrated the presence of herpes virus particles. MCMV DNA and glycoprotein B were demonstrated in the epithelial cells of the lung tissue in those animals by in situ hybridization and immunohistochemistry, respectively. Our data demonstrated the establishment of a mouse model of interstitial pneumonitis via MCMV infection after allogeneic skin transplantation. © 2013 Dequn Ni et al.


Riveira-Munoz E.,Genomic Health | He S.-M.,Anhui University | He S.-M.,Key Laboratory of Gene Resource Utilization for Severe Diseases | He S.-M.,Anhui Medical University | And 51 more authors.
Journal of Investigative Dermatology | Year: 2011

A multicenter meta-analysis including data from 9,389 psoriasis patients and 9,477 control subjects was performed to investigate the contribution of the deletion of genes LCE3C and LCE3B, involved in skin barrier defense, to psoriasis susceptibility in different populations. The study confirms that the deletion of LCE3C and LCE3B is a common genetic factor for susceptibility to psoriasis in the European populations (OROverall=1.21 (1.15-1.27)), and for the first time directly demonstrates the deletion's association with psoriasis in the Chinese (OR=1.27 (1.16-1.34)) and Mongolian (OR=2.08 (1.44-2.99)) populations. The analysis of the HLA-Cw6 locus showed significant differences in the epistatic interaction with the LCE3C and LCE3B deletion in at least some European populations, indicating epistatic effects between these two major genetic contributors to psoriasis. The study highlights the value of examining genetic risk factors in multiple populations to identify genetic interactions, and indicates the need of further studies to understand the interaction of the skin barrier and the immune system in susceptibility to psoriasis. © 2011 The Society for Investigative Dermatology.

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