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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.


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.


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 53 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.


Luo B.F.,Centers for Disease Control and Prevention | Du L.,Centers for Disease Control and Prevention | Li J.X.,Peking University | Pan B.Y.,Centers 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.


Yu H.,Anhui Medical University | Yu H.,Key Laboratory of Gene Resource Utilization for Severe Diseases | Chen W.,Anhui Medical University | Chen W.,Key Laboratory of Gene Resource Utilization for Severe Diseases | And 14 more authors.
Virus Genes | Year: 2010

Enterovirus 71 (EV71) strains from children were characterized by full-length VP1 nucleotide sequencing. Out of 22 clinical specimens, five isolates identified as EV71 were recovered by virus isolation. The VP1 sequences of the five isolates had more than 97.4% sequence identity with prototype virus BrCr, clustering in the genotype A lineage. This represents the first record of genotype A EV71 in China since the BrCr prototype strain was discovered in the USA in 1969. © 2010 Springer Science+Business Media, LLC.


Yu H.,Anhui Medical University | Yu H.,Key Laboratory of Gene Resource Utilization for Severe Diseases | Wang M.,Anhui Medical University | Wang M.,Key Laboratory of Gene Resource Utilization for Severe Diseases | And 18 more authors.
Japanese Journal of Infectious Diseases | Year: 2011

We performed preepidemic and postepidemic serological surveys to elucidate the rate of enterovirus 71 (EV71) infection in Lu'an City, Anhui Province, Central China. For the preepidemic study, a total of 472 healthy infants and children (age range, neonates to 15 years) were randomly selected before the 2008 outbreak of EV71 in the region. Blood samples were collected and tested for neutralizing antibodies (NAbs) against EV71 by performing a microneutralization assay. The results of preepidemic serological survey showed that 43.2z (204/472) of the tested samples yielded positive results for NAbs against EV71. The seropositivity rates were 29.6z (93/314) in children who were 0-7 years of age and 74.6z (59/79) in children who were 12-15 years of age. The overall geometric mean titer was 18.1, and the highest antibody titers were detected in children who were 5-7 years of age; this suggests that this group was frequently exposed to EV71 infection. For Ã15 years of age in 2010. The seropositivity rate of EV71 NAbs increased in this young population after the 2008 outbreak, especially in 2- to 11-year-old children. This report shows that EV71 was spreading in Lu'an City before the 2008 outbreak, and children under 7 years of age were the main susceptible population.


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.


Li X.,Anhui Medical University | Li X.,Key Laboratory of Gene Resource Utilization for Severe Diseases | Shen J.,Anhui Medical University | Shen J.,Key Laboratory of Gene Resource Utilization for Severe Diseases | And 10 more authors.
Parasitology | Year: 2010

Treatment of liver fibrosis associated with Schistosoma japonicum ova-induced granulomas remains a challenging proposition. Paeoniflorin (PAE, C23H28O11) has anti-inflammatory, anti-allergic, and immunoregulatory effects and it is commonly used in Chinese Herbal prescriptions to treat hepatic disorders. The present study was carried out to investigate the effects of PAE on hepatic fibrosis of mice infected with S. japonicum and to explore its possible mechanism. Upon pathological examination of PAE-treated mice, the size of egg granuloma, fibrosis scores, the concentration of IL-13 and hydroxyproline in liver were significantly reduced compared with the model mice. In the primary culture of hepatic stellate cells (HSCs), PAE inhibited IL-13-induced collagen synthesis. These results suggested that PAE might alleviate the hepatic granulomas and fibrosis caused by S. japonicum and the inhibitory effect of PAE on hepatic fibrosis might be associated with its ability to decrease the level of IL-13 and to interfere with the IL-13 signalling molecule in HSCs. Copyright © 2010 Cambridge University Press.

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