15 research outputs found
Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians
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
Translation and validation of the Hong Kong Chinese version of the pediatric quality of life inventoryTM (PedsQLTM) end-stage renaldisease module
Objective
The goal of this study is to report on the linguistic validation and reliability of the Hong Kong Chinese version of the Pediatric Quality of Life Inventory™ (PedsQL™) End-stage Renal Disease Module for Children with end-stage renal disease (ESRD) in Hong Kong, and its use to assess health-related quality of life (HRQOL) in end-stage renal disease children receiving different treatment modalities: peritoneal dialysis, haemodialysis and renal transplantation.
Methods
In part 1, forward and backward translations following a stringent validation protocol produced the Chinese translation version. Content validity of the translated instrument was assessed. In part 2, internal consistency and reliability of the questionnaire was evaluated by 38 pairs of parents and children with end-stage renal disease aged 5 to 18. The data was further analysed according to different treatment modalities.
Results
The translated Hong Kong Chinese version of the Pediatric Quality of Life Inventory ™ (PedsQL™) End-stage Renal Disease Module (PedsQL™ 3.0 ESRD Module-HKC) was found to have good content validity and was acceptable to most patients and parents. Internal consistency was excellent (Cronbach’s α = 0.91 in Patient version and = 0.94 in Parent version). Test-retest reliability, determined with the intraclass correlation coefficients, was excellent (0.89 in Patient version and 0.93 in Parent version). It was found that there was significant better HRQOL in patient received renal transplantation compared with Dialysis (peritoneal dialysis or haemodialysis, p=0.006.)
Conclusions
This study suggested good content validity, internal consistency, and reliability of the Chinese version of the Pediatric Quality of Life Inventory ™ (PedsQL™) End-stage Renal Disease Module (PedsQL™ 3.0 ESRD Module-HKC). It opened a new dimension of health care assessment for end-stage renal disease children in Hong Kong. Transplantation was reported to have a significant better quality of life score. Further studies with larger samples should be performed to confirm the psychometric properties of this translated instrument.published_or_final_versionPublic HealthMasterMaster of Public Healt
Real-Time Intraocular Pressure Measurements in the Vitreous Chamber of Rabbit Eyes During Small Incision Lenticule Extraction (SMILE)
A standardized technique of laparoscopic placement of peritoneal dialysis catheter with omentectomy and closure of patent processus vaginalis: A 3-in-1 minimally invasive surgical approach in children
Imaging studies for first urinary tract infection in infants less than 6 months old: can they be more selective?
Erratum to: Lupus nephritis in Chinese children — a territory-wide cohort study in Hong Kong
MDSCs drive the process of endometriosis by enhancing angiogenesis and are a new potential therapeutic target
Endometriosis affects women of reproductive age via unclear immunological mechanism(s). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid cells with potent immunosuppressive and angiogenic properties. Here, we found MDSCs significantly increased in the peripheral blood of patients with endometriosis and in the peritoneal cavity of a mouse model of surgically induced endometriosis. Majority of MDSCs were granulocytic, produced ROS, and arginase, and suppressed T-cell proliferation. Depletion of MDSCs by antiGr-1 antibody dramatically suppressed development of endometrial lesions in mice. The chemokines CXCL1, 2, and 5 were expressed at sites of lesion while MDSCs expressed CXCR-2. These CXC-chemokines promoted MDSC migration toward endometriotic implants both in vitro and in vivo. Also, CXCR2-deficient mice show significantly decreased MDSC induction, endometrial lesions, and angiogenesis. Importantly, adoptive transfer of MDSCs into CXCR2-KO mice restored endometriotic growth and angiogenesis. Together, this study demonstrates that MDSCs play a role in the pathogenesis of endometriosis and identifies a novel CXC-chemokine and receptor for the recruitment of MDSCs, thereby providing a potential target for endometriosis treatment
Three SNPs in chromosome 11q23.3 are independently associated with systemic lupus erythematosus in Asians
Systemic lupus erythematosus (SLE) has a complex etiology and is affected by both genetic and environmental factors. Althoughmorethan 40 loci haveshownrobust association withSLE, the details of these loci,suchas the independent contributors and the genes involved, are still unclear. In this study, we performed meta-analysis of two existing genome-wide association studies (GWASs) on Chinese Han populations from Hong Kong and Anhui, China, and followed the findings by further replication on three additional Chinese and Thailand cohorts with a total of 4254 cases and 6262 controls matched geographically and ethnically. We discovered multiple susceptibility variants for SLE in the 11q23.3 region, including variants in/near PHLDB1 (rs11603023, P_combined 5 1.25E208, OR 5 1.20), DDX6 (rs638893, P_combined 5 5.19E207, OR 5 1.22) and CXCR5 (rs10892301, P_combined 5 2.51E208, OR 5 0.85). Genetic contributions from the newly identified variants were all independent of SNP rs4639966, whose association was reported from the previous GWAS. In addition, the three newly identified variants all showed independent association with the disease through modeling by both stepwise and conditional logistic regression. The presence of multiple independent variants in this region emphasizes its role in SLE susceptibility, and also hints the possibility that distinct biological mechanisms might be involved in the disease involving this genomic region. © The Author 2013. Published by Oxford University Press. All rights reserved.Link_to_subscribed_fulltex
Meta-analysis of GWAS on two Chinese populations followed by replication identifies novel genetic variants on the X chromosome associated with systemic lupus erythematosus
© The Author 2014. Published by Oxford University Press. All rights reserved. Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that affects mainly females. What role the X chromosome plays in the disease has always been an intriguing question. In this study, we examined the genetic variants on the X chromosome through meta-analysis of two genome-wide association studies (GWAS) on SLE on Chinese Han populations. Prominent association signals from the meta-analysis were replicated in 4 additional Asian cohorts, with a total of 5373 cases and 9166 matched controls. We identified a novel variant in PRPS2 on Xp22.3 as associated with SLE with genome-wide significance (rs7062536, OR = 0.84, P = 1.00E-08). Association of the L1CAM-MECP2 region with SLE was reported previously. In this study, we identified independent contributors in this region in NAA10 (rs2071128, OR = 0.81, P = 2.19E-13) and TMEM187 (rs17422, OR = 0.75, P = 1.47E-15), in addition to replicating the association from IRAK1-MECP2 region (rs1059702, OR = 0.71, P = 2.40E-18) in Asian cohorts. The X-linked susceptibility variants showed higher effect size in males than that in females, similar to results from a genome-wide survey of associated SNPs on the autosomes. These results suggest that susceptibility genes identified on the X chromosome, while contributing to disease predisposition, might not contribute significantly to the female predominance of this prototype autoimmune disease.Link_to_subscribed_fulltex