Hong Zhang

Huazhong University of Science and Technology, Wu-han-shih, Hubei, China

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Publications (143)574.58 Total impact

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    ABSTRACT: Systemic lupus erythematosus (SLE) has a strong but incompletely understood genetic architecture. We conducted an association study with replication in 4,478 SLE cases and 12,656 controls from six East Asian cohorts to identify new SLE susceptibility loci and better localize known loci. We identified ten new loci and confirmed 20 known loci with genome-wide significance. Among the new loci, the most significant locus was GTF2IRD1-GTF2I at 7q11.23 (rs73366469, Pmeta = 3.75 × 10(-117), odds ratio (OR) = 2.38), followed by DEF6, IL12B, TCF7, TERT, CD226, PCNXL3, RASGRP1, SYNGR1 and SIGLEC6. We identified the most likely functional variants at each locus by analyzing epigenetic marks and gene expression data. Ten candidate variants are known to alter gene expression in cis or in trans. Enrichment analysis highlights the importance of these loci in B cell and T cell biology. The new loci, together with previously known loci, increase the explained heritability of SLE to 24%. The new loci share functional and ontological characteristics with previously reported loci and are possible drug targets for SLE therapeutics.
    Full-text · Article · Jan 2016 · Nature Genetics
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    ABSTRACT: Aberrant activation of the hedgehog (Hh) signaling pathway has shown predictive significance for treatment response and prognostic effect for survival in human tumors. However, the associations of the Hh signaling pathway with response to neoadjuvant therapy (NAT) and survival after NAT in breast cancer are unknown. Therefore, we investigated the correlation of pretherapeutic nuclear expression of glioma-associated oncogene homolog 1 (Gli1), a key transcriptional factor of the Hh signaling pathway, with pathological complete response (pCR) and event-free survival (EFS) in HER2-positive breast cancer treated with trastuzumab-based NAT. High nuclear Gli1 expression (OR 0.19; 95 % CI 0.07-0.54; P = 0.002) and positive hormone receptor (HR) status (OR 0.36; 95 % CI 0.14-0.90; P = 0.028) were independent and negative predictors of pCR in multivariate analysis. High nuclear Gli1 expression was significantly associated with lower pCR rates in both HR-positive and HR-negative tumors (P = 0.014 and 0.024, respectively). For survival analyses, multivariate analysis indicated that high nuclear Gli1 expression was the only independent predictor of poorer EFS in both the entire population (hazard ratio 2.97; 95 % CI 1.18-7.44; P = 0.020) and patients with non-pCR (hazard ratio 3.98; 95 % CI 1.35-11.68; P = 0.012). Our study is the first to demonstrate the associations of high nuclear Gli1 expression with resistance to trastuzumab-based NAT and subsequent worse prognosis in HER2-positive disease. These findings suggest that the nuclear Gli1 protein may be a novel target of NAT for HER2-positive breast cancer.
    No preview · Article · Nov 2015 · Tumor Biology
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    ABSTRACT: The purpose of the present study was to determine the optimal threshold for stromal tumor-infiltrating lymphocytes (TILs) and investigate its predictive and prognostic value in HER2-positive breast cancer treated with trastuzumab-based neoadjuvant chemotherapy (NAC). Levels of stromal TILs were evaluated using hematoxylin and eosin-stained sections of core biopsies from 116 patients. We investigated the correlation between stromal TILs and pathological response to identify its optimal threshold. Using receiver operating characteristic curve analysis, a 30 % threshold best discriminated pathological complete response (pCR) from non-pCR subgroups (P < 0.001). Lymphocyte-rich breast cancer (LRBC) was defined as having ≥30 % stromal TILs level, and was used for analysis. For analyses of predictive factors, multivariate analysis indicated that LRBC was a strong predictor of pCR with an odds ratio of 5.23 (P < 0.001). Negative hormone receptor (HR) status was also significantly associated with pCR (P = 0.028). LRBC significantly predicted pCR in both HR-positive and HR-negative tumors (P = 0.016 and 0.006, respectively). For survival analyses, LRBC was the only independent predictor of improved event-free survival (EFS) among baseline clinicopathological factors in multivariate analysis (P = 0.012). When pathological response was included, both LRBC and pCR were independent predictors of better EFS (P = 0.040 and 0.045, respectively). LRBC significantly predicted longer EFS in the non-pCR subgroup (P = 0.018), whereas LRBC was not significantly associated with EFS in the pCR subgroup (P = 0.825). A 30 % threshold for stromal TILs optimally identified response to trastuzumab-based NAC in HER2-positive breast cancer; its predictive and prognostic value was also validated in our study.
    No preview · Article · Oct 2015 · Breast Cancer Research and Treatment
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    ABSTRACT: Background and objectives: We undertook a systematic review and meta-analysis of published cohort studies and case-control studies to estimate (1) the risk of pregnancy complications among patients with CKD versus those without CKD and (2) the risk of CKD progression among pregnant patients versus nonpregnant controls with CKD. Design, setting, participants, & measurements: We searched electronic databases for studies published between 1946 and 2014, and we reviewed articles using validity criteria. Random-effects analytical methods were used. Results: Twenty-three studies (14 with data for adverse pregnancy outcomes and 9 for renal outcomes) with 506,340 pregnancies were included. Pregnancy with CKD had greater odds of preeclampsia (odds ratio [OR], 10.36; 95% confidence interval [95% CI], 6.28 to 17.09), premature delivery (OR, 5.72; 95% CI, 3.26 to 10.03), small for gestational age/low birth weight (OR, 4.85; 95% CI, 3.03 to 7.76), cesarean section (OR, 2.67; 95% CI, 2.01 to 3.54), and failure of pregnancy (OR, 1.80; 95% CI, 1.03 to 3.13). Subgroup analysis showed that odds of preeclampsia (P<0.01) and premature delivery (P<0.01) were higher in women with nondiabetic nephropathy compared with diabetic nephropathy, and the odds of preeclampsia (P=0.01) and premature delivery (P<0.01) were higher in women with macroproteinuria compared with microproteinuria. The median for follow-up time for renal events was 5 years (interquartile range, 5-14.7 years). There were no significant differences in the occurrence of renal events between CKD pregnant women and those without pregnancy (OR, 0.96; 95% CI, 0.69 to 1.35). Subgroup analysis showed that publication year, sample size, follow-up years, type of primary disease, CKD classification, level of serum creatinine at baseline, proteinuria, and level of systolic BP did not modify the renal outcomes. Conclusions: The risks of adverse maternal and fetal outcomes in pregnancy are higher for women with CKD versus pregnant women without CKD. However, pregnancy was not a risk factor for progression of renal disease in women with CKD before pregnancy.
    No preview · Article · Oct 2015 · Clinical Journal of the American Society of Nephrology
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    ABSTRACT: Objectives . Numerous loci were identified to perturb gene expression in trans . As elevated ATG5 expression was observed in systemic lupus erythematosus (SLE), the study was conducted to analyze the genome-wide genetic regulatory mechanisms associated with ATG5 expression in a Chinese population with lupus nephritis (LN). Methods . The online expression quantitative trait loci database was searched for trans -expression single nucleotide polymorphisms ( trans -eSNPs) of ATG5 . Tagging trans -eSNPs were genotyped by a custom-made genotyping chip in 280 patients and 199 controls. For positive findings, clinical information and bioinformation analyses were performed. Results . Four trans -eSNPs were observed to be associated with susceptibility to LN ( P < 0.05), including ANKRD50 rs17008504, AGA rs2271100, PAK7 rs6056923, and TET2 rs1391441, while seven other trans -eSNPs showed marginal significant associations (0.05 < P < 0.1). Correlations between the trans -eSNPs and ATG5 expression and different expression levels of ATG5 in SLE patients and controls were validated, and their regulatory effects were annotated. However, no significant associations were observed between different genotypes of trans -eSNPs and severity or outcome of the patients. Conclusion . Using the new systemic genetics approach, we identified 10 loci associated with susceptibility to LN potentially, which may be complementary to future pathway based genetic studies.
    Full-text · Article · Oct 2015 · Journal of Immunology Research
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    ABSTRACT: Background: The coexistence of IgA nephropathy (IgAN) and antineutrophil cytoplasmic autoantibodies (ANCAs) is relatively rare. Only a few studies have reported the features of these patients. Methods: We studied the clinical and histological features of 20 ANCA-positive IgAN patients. They were compared with ANCA-negative IgAN patients (n = 40) and ANCA-associated systemic vasculitis (AASV) patients (n = 40) with a randomly selected and matched proportion of crescentic glomeruli. Furthermore, 9 ANCA-positive crescentic IgAN patients out of the 20 cases were compared with two control groups with crescentic nephritis. Results: ANCA-positive IgAN patients showed older age, lower haemoglobin and higher inflammatory indicator levels at baseline, and a higher percentage of general symptoms and pulmonary involvement, compared with ANCA-negative IgAN patients, and were comparable to AASV patients. Histologically, there was a significantly higher percentage of fibrinoid necrosis in glomeruli in ANCA-positive IgAN patients and in AASV patients compared with ANCA-negative IgAN patients (35, 25 and 0%, respectively, P = 0.003). After immunosuppressive therapy, ANCA-positive crescentic IgAN patients were more likely to withdraw from dialysis (75 versus 9.1%, P = 0.03) and not to reach end-stage renal disease within 6 months (11.1 versus 66.7%, P = 0.01) compared with ANCA-negative crescentic IgAN patients. Conclusions: IgAN patients with ANCA positivity showed more severe clinical and histological features when compared with ANCA-negative IgAN patients and were comparable to AASV patients. However, renal prognosis was relatively better in ANCA-positive crescentic IgAN patients after aggressive immunosuppressive therapy in the short term, compared with ANCA-negative patients.
    Preview · Article · Oct 2015 · CKJ: Clinical Kidney Journal
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    Full-text · Article · Jul 2015 · Arthritis and Rheumatology
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    ABSTRACT: Recently, common variants within or near ATG5, which is a key autophagy gene required for the formation of autophagosomes, have been identified as a candidate gene of systemic lupus erythematosus (SLE) by several genome-wide association studies. Moreover, elevated ATG5 expression was observed in SLE as well as other autoimmune diseases. However, no significant associations between variants within ATG5 and SLE were identified in several Chinese populations. The present study was conducted to further check the genetic role of ATG5 by associating both common and rare variants of ATG5 in Chinese patients with lupus nephritis (LN), a major phenotype with poor prognosis in SLE. To detect the association of common variants of ATG5 with LN, 7 tagging single nucleotide polymorphisms (SNPs) designed in immunochip and 4 SNPs reported to be associated with SLE were genotyped in 500 LN patients and 500 healthy controls. Furthermore, direct sequencing of exons and their flanking regions in 90 LN patients, 30 SLE patients, and 60 healthy controls were performed. Functional genomic annotation was performed by using public databases. None of the 11 tagging SNPs was observed to be associated with LN. By sequencing, 13 variants were identified, including 5 common SNPs, 7 not previously described, and 1 reported as rare variants (<1%) in the Single Nucleotide Polymorphism Database or the 1000 Genome project. None of the 5 common SNPs showed significant association between patients and controls, whereas increased frequencies of rare or novel variants were observed in patients compared with healthy controls, with 6/90 in LN patients, 2/30 in SLE patients, and 1/163 in healthy controls. Although these rare variants were observed to be located in the flanking regions of exons instead of missense mutations, patients carrying them tended to have severe clinical phenotype, and in silicon analysis suggested their regulatory effects. Increased frequencies of rare variants of ATG5 were identified in patients with LN and SLE compared with healthy controls, highlighting a likely important role of rare ATG5 variants in Chinese SLE patients.
    Full-text · Article · Jun 2015 · Medicine
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    ABSTRACT: IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. Previously identified genome-wide association study (GWAS) loci explain only a fraction of disease risk. To identify novel susceptibility loci in Han Chinese, we conduct a four-stage GWAS comprising 8,313 cases and 19,680 controls. Here, we show novel associations at ST6GAL1 on 3q27.3 (rs7634389, odds ratio (OR)=1.13, P=7.27 × 10(-10)), ACCS on 11p11.2 (rs2074038, OR=1.14, P=3.93 × 10(-9)) and ODF1-KLF10 on 8q22.3 (rs2033562, OR=1.13, P=1.41 × 10(-9)), validate a recently reported association at ITGAX-ITGAM on 16p11.2 (rs7190997, OR=1.22, P=2.26 × 10(-19)), and identify three independent signals within the DEFA locus (rs2738058, P=1.15 × 10(-19); rs12716641, P=9.53 × 10(-9); rs9314614, P=4.25 × 10(-9), multivariate association). The risk variants on 3q27.3 and 11p11.2 show strong association with mRNA expression levels in blood cells while allele frequencies of the risk variants within ST6GAL1, ACCS and DEFA correlate with geographical variation in IgAN prevalence. Our findings expand our understanding on IgAN genetic susceptibility and provide novel biological insights into molecular mechanisms underlying IgAN.
    Full-text · Article · Jun 2015 · Nature Communications
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    Xu-Jie Zhou · Hong Zhang

    Full-text · Article · May 2015 · Rheumatology (Oxford, England)
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    ABSTRACT: Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10−33), we observed one SNP showing significant association to POAG (CDC7–TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10−8). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.
    Full-text · Article · Apr 2015 · Human Molecular Genetics
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    ABSTRACT: To retrospectively evaluate the HER2 status of 1 501 invasive breast cancer (IBC) by immunohistochemistry (IHC) and fluorescent in situ hybridizaion (FISH), and to compare and analyze the changes and their effects, using the 2007 and 2013 American Society of Clinical Oncology/College of American Pathologist(ASCO/CAP) HER2 testing guidelines. Tissue handling and HER2 testing were performed according the 2007 ASCO/CAP guideline recommendations. The HER2 status of all newly diagnosed IBC were routinely assessed by IHC, and reflex FISH assay was done on all the IHC equivocal (IHC 2+) cases. The HER2 status of 1 501 cases of IBC was re-evaluated according to these two criteria. Using the 2007 and 2013 ASCO/CAP criteria, the overall positive, equivocal and negative rates of HER2 over-expression and/or amplification in the 1 501 IBCs were 23.05% and 23.52%, 11.59% and 12.52%, and 65.36% and 63.96%, respectively. The positive and equivocal rates increased by 0.47% and 0.93% respectively, but the negative rate decreased by 1.40% when using the new criteria. For HER2 IHC staining using the 2007 and 2013 guidelines, the positive, equivocal and negative rates were 17.99% and 18.13% (+0.13%), 32.51% and 32.91% (+0.40%) and 49.50% and 48, 97% (-0.53%), respectively. FISH for HER2 amplification was done in 348 of the 1 501 IBCs, and using the 2007 and 2013 guidelines, the positive, equivocal and negative rates were 27.59% and 29.02% (+1.43%), 1.15% and 3.74% (+2.59%) and 71.26% and 67.24% (-4.02%), respectively. The application of 2013 ASCO/CAP guideline could lead to an increase in positive and equivocal rates, and a decrease in negative rate. The influence could be more prominent for the evaluation of FISH result, and would raise the positive and equivocal rates since a mean HER2 copy number is used in the new criteria. Our re-estimation of IHC result was concordant with the prediction of the guideline.
    No preview · Article · Mar 2015 · Zhonghua bing li xue za zhi Chinese journal of pathology
  • Lei Yu · Ping Hou · Ji‐Cheng Lv · Guo‐Ping Liu · Hong Zhang
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    ABSTRACT: Familial renal glucosuria (FRG) is characterized by persistent glucosuria despite normal serum glucose and the absence of overt tubular dysfunction. Variants in solute carrier family 5 (sodium-glucose co-transporter), member 2 (SLC5A2) have been reported in FRG patients. However, the functional and expression-related consequences of such variants have been scarcely investigated. In the current study, we studied five FRG families and identified six missense mutations, including four novel variants (c.1051T>C/p.(C351R), c.1400T>C/p.(V467A), c.1420G>C/p.(A474P), c.1691G>A/p.(R564Q); RNA not analyzed) and two variants that had been previously reported (c.294C>A/p.(F98L), c.736C>T/p.(P246S); RNA not analyzed). The probands were either heterozygous or compound heterozygous for SLC5A2 variants and had glucosuria of 5.9–19.6 g/day. Human 293 cells were transfected with plasmid constructs to study the expression and function of SLC5A2 Variants in vitro. Western blotting revealed that the expression levels of SLC5A2–351R-GFP, SLC5A2–467A-GFP, SLC5A2–474P-GFP and SLC5A2–564Q-GFP were significantly decreased compared with wild-type SLC5A2-GFP (37–55%). Confocal microscopy revealed that three variants (c.1400T>C, c.1420G>C, c.1691G>A) resulted in a loss of the punctate membrane pattern typical of wild-type SLC5A2. All Variants had a significantly lower transport capacity in than the wild-type control. The current study provides a starting point to further investigate the molecular mechanism of SLC5A2 in FRG families and provides functional clues for anti-diabetes drugs.This article is protected by copyright. All rights reserved
    No preview · Article · Jan 2015 · Human Mutation
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    ABSTRACT: To evaluate the value of ultrasound (US) in predicting axilla status and to investigate the clinic pathologic characters in the axillary node metastasis. From June 2012 to June 2013, 323 female primary breast cancer patients who received both axilla ultrasound and pathology examinations were reviewed retrospectively. The features of axillary nodes including diameter, longitudinal-transverse axis ratio, cortical thickness and blood flow grade were used to evaluate axillary status. US accuracy of axillary node metastasis was analyzed correlated with the final pathology results. The clinical and histological features associated with axillary node metastasis was analyzed by χ(2) test. The proportions of Luminal A-like, Luminal B-like, human epidermalgrowth factor receptor-2 positive and triple negative breast cancer were 11.1% (36/323), 58.5% (189/323), 13.3% (43/323) and 17.0% (55/323) . The sensitivity, specificity, positive predictive value and negative predictive value of axilla US in the diagnosis of nodal metastasis were 35.6% (46/129), 98.9% (181/183), 95.8% (46/48) and 68.6% (181/264). Axillary lymph node metastasis had statistically significant correlation with menopausal status and clinical tumor size (χ(2) = 4.337, 11.100; P = 0.037, 0.001). Standardized ultrasound is the basic way to evaluate axilla status. Sentinel lymph node biopsy should be done to acquire accurate preoperative staging of axilla when US shows no signs of metastasis. Axillary lymph node metastasis is significantly related to menopausal status and clinical tumor size, but not significantly related to subtype classification of primary breast cancer.
    No preview · Article · Dec 2014 · Zhonghua wai ke za zhi [Chinese journal of surgery]
  • Shuang Zhang · Ying Wang · Z M Guo · Hong Zhang · Ling Xu · Y H Liu · Ting Li
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    ABSTRACT: Objective: To study the evaluation of human epithelial growth factor receptor 2 (HER2) status in breast carcinoma with amplified chromosome 17 centromere locus (CEP17) and clinical significance of CEP17 amplification. Methods: Two hundred-eighteen cases of breast carcinoma were collected. We performed immunohistochemistry (IHC) to test HER2 protein and fluorescence in situ hybridization (FISH) to evaluate HER2 gene status. Results: Two cases in this cohort manifested CEP17 amplification. HER2 signals for case 1 was countable, and the average number was 2.6 per one nuclei, and the signals of CEP17 were clustered or multipunctiform. This case was evaluated as no HER2 amplification, but with amplified CEP17 . In case 2 the signals of HER2 and CEP17 were countable, and the average number of HER2 signal was 6.8 per one nucleus while CEP17 signal was 5.9 per one nucleus. The status was considered as HER2 and CEP17 coamplification. And the levels of HER2 protein expression of these two cases were both two plus. Conclusion: The incidence of CEP17 amplification in breast carcinoma is rare, with or without HER2 amplification. We recommend to evaluate the exact HER2 status by the HER2 copy number, and should also analyze the HER2/CEP17 ratio and the level of HER2 protein, for providing more accurate evidence to support the clinical target therapy.
    No preview · Article · Oct 2014 · Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences
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    ABSTRACT: Abstract We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN.
    Full-text · Article · Oct 2014 · Nature Genetics
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    ABSTRACT: Objective Several novel susceptibility genes for systemic lupus erythematosus (SLE) and IgA nephropathy have been identified in recent genome-wide association studies. Since both lupus nephritis and IgA nephropathy are autoimmune diseases of the kidney, they may share common disease mechanisms that overlap with genetic susceptibility. To test this hypothesis, we sought to identify genetic variants associated with IgA nephropathy in lupus nephritis. Methods In the first stage, 500 patients with lupus nephritis, 240 SLE patients without nephritis, and 500 healthy controls were enrolled. Fifteen single-nucleotide polymorphisms (SNPs) that had the topmost association signals with IgA nephropathy were selected for further testing in patients with lupus nephritis. Three independent cohorts from Beijing, Shanghai, and Hong Kong were included as replicates. We also analyzed the functional significance of identified noncoding variants on regulatory motifs and gene expression. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. ResultsIn addition to associations with HLA gene polymorphisms, genetic variants of MTMR3 in 22q12 showed associations with lupus nephritis (for rs9983A, OR 1.61 [95% CI 1.19-2.19], P = 2.07 x 10(-3)) compared to healthy controls in the first stage. Associations were replicated and reinforced among northern Han Chinese (for lupus nephritis patients versus SLE patients without nephritis, P = 0.01) but not southern Han Chinese, although significant genetic heterogeneity was observed. Conservative and regulatory features of rs9983 were predicted in in silico analyses. In expression analysis, we observed lower MTMR3 transcription levels in samples of blood with rs9983A and in renal biopsy samples from lupus nephritis and IgA nephropathy patients. Conclusion Our results suggest that the MTMR3 gene is shared between IgA nephropathy and lupus nephritis in the northern Chinese population, further highlighting the role of autophagy in SLE. However, widespread replication of these experiments, fine mapping, and functional assays are required to establish this connection.
    Full-text · Article · Oct 2014 · Arthritis and Rheumatology
  • Ling Xin · Hong Zhang · Shuang Zhang · Jingming Ye · Ting Li · Yinhua Liu

    No preview · Article · Oct 2014 · Chinese medical journal
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    ABSTRACT: Complement activation is common in patients with IgA nephropathy (IgAN) and associated with disease severity. Our recent genome-wide association study of IgAN identified susceptibility loci on 1q23 containing the complement regulatory protein-encoding genes CFH and CFHR1-5, with rs6677604 in CFH as the top single-nucleotide polymorphism and CFHR3-1 deletion (CFHR3-1∆) as the top signal for copy number variation. In this study, to explore the clinical effects of variation in CFH, CFHR3, and CFHR1 on IgAN susceptibility and progression, we enrolled two populations. Group 1 included 1178 subjects with IgAN and available genome-wide association study data. Group 2 included 365 subjects with IgAN and available clinical follow-up data. In group 1, rs6677604 was associated with mesangial C3 deposition by genotype-phenotype correlation analysis. In group 2, we detected a linkage between the rs6677604-A allele and CFHR3-1∆ and found that the rs6677604-A allele was associated with higher serum levels of CFH and lower levels of the complement activation split product C3a. Furthermore, CFH levels were positively associated with circulating C3 levels and negatively associated with mesangial C3 deposition. Moreover, serum levels of the pathogenic galactose-deficient glycoform of IgA1 were also associated with the degree of mesangial C3 deposition in patients with IgAN. Our findings suggest that genetic variants in CFH, CFHR3, and CFHR1 affect complement activation and thereby, predispose patients to develop IgAN.
    No preview · Article · Sep 2014 · Journal of the American Society of Nephrology
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    ABSTRACT: Objective Human neutrophil peptides (HNP) were recently implicated in the neutrophil extracellular trap (NET) complex, the impaired degradation of which has been associated with lupus nephritis (LN).Methods Forty LN patients, 40 SLE patients without kidney injury, 63 immunoglobulin A nephropathy (IgAN) patients, 20 minimal change disease (MCD) patients and 33 healthy controls were included in the present study. LN, IgAN and MCD patients were diagnosed with renal biopsy. LN patients were followed for a median period of 5.5 years. Clinical and laboratory data at the time of renal biopsy and follow-up were collected for each LN patient. Serum levels of HNP1–3 were measured with enzyme-linked immunosorbent assay.ResultsSerum HNP1-3 levels in LN patients were significantly higher than for SLE patients without kidney injury (P < 0.001), IgAN patients (P = 0.012), MCD patients (P = 0.010) and healthy controls (P = 0.022). Serum HNP1–3 levels were an independent indicator of LN (P = 0.006, OR = 7.5, 95% CI, 1.782–31.842), were statistically correlated with urinary protein excretion (P = 0.009) and activity index (P = 0.042) and were only marginally correlated with neutrophils (P = 0.054) and white blood cell counts (P = 0.051). Serum levels of HNP1–3 were a predictor of proteinuria remission after correction for multiple parameters (multivariate hazard 0.209; 95% CI 0.046–0.951; P = 0.043).Conclusions The data from this study indicated that HNP1–3, one component of the NET, is a potential biomarker for LN.
    No preview · Article · Aug 2014 · International Journal of Rheumatic Diseases

Publication Stats

3k Citations
574.58 Total Impact Points


  • 2010-2015
    • Huazhong University of Science and Technology
      • • Department of Ophthalmology
      • • Key Laboratory of Molecular Biophysics, MOE
      • • Key Laboratory of Molecular Biophysics of Ministry of Education
      Wu-han-shih, Hubei, China
  • 2003-2015
    • Peking University
      • Institute of Urology
      Peping, Beijing, China
  • 1999-2015
    • Beijing Medical University
      • • Department of Pathology
      • • Department of Medicine
      • • Department of Respiratory Medicine
      • • Department of Internal Medicine
      Peping, Beijing, China
  • 2014
    • Peking University Health Science Center
      Peping, Beijing, China
  • 2013
    • Shandong University
      Chi-nan-shih, Shandong Sheng, China
  • 2007-2013
    • Anhui Medical University
      • • Department of Epidemiology and Biostatistics
      • • Department of Pathology
      Luchow, Anhui Sheng, China
  • 2000-2002
    • Okayama University
      • Department of Medicine and Clinical Science
      Okayama, Okayama, Japan