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Autoimmunity | 2013

Association study of glucocorticoid receptor genetic polymorphisms with efficacy of glucocorticoids in systemic lupus erythematosus: A prospective cohort study

Yan-Feng Zou; Jianhua Xu; Fen Wang; Shuang Liu; Jin-Hui Tao; Jing Cai; Li Lian; Hui Xiao; Pei-Ling Chen; Guo Tian; Min Wu; De-Guang Wang; Sheng-Xiu Liu; Chun-Mei Liang; Faming Pan; Hong Su; Hai-Feng Pan; Dong-Qing Ye

Abstract The response to glucocorticoids (GCs) for patients with systemic lupus erythematosus (SLE) is characterized by wide interindividual variability, with a significant number of patients who have no response. We analyzed whether genetic polymorphisms within glucocorticoid receptor (GR) gene are related to variability in the efficacy of GCs in Chinese population with SLE. A cohort of 220 patients with SLE was studied. These patients were treated with GCs (prednisone) for 12 weeks. The efficacy of GCs was measured with the scores on SLE disease activity index (SLEDAI). Patients were classified into two groups (sensitive and insensitive) according to their response to GCs. Polymorphisms of GR gene were genotyped by using multiplex SNaPshot method. A total of 212 patients (96.4%) were included in the final data analyses. Of these patients, 110 patients were considered sensitive to GCs, and 102 patients were considered insensitive to GCs. Eighteen tag single nucleotide polymorphisms (SNPs) of GR gene were selected. Significant associations were seen for rs4912905 (dominant model: crude OR = 0.410, 95%CI = 0.233–0.722, p = 0.002; adjusted OR = 0.419, 95%CI = 0.233–0.754, p = 0.004), rs17100234 (dominant model: crude OR = 0.521, 95%CI = 0.282–0.963, p = 0.038; adjusted OR = 0.520, 95%CI = 0.279–0.970, p = 0.040) and rs7701443 (recessive model: crude OR = 2.736, 95%CI = 1.183–6.331, p = 0.019; adjusted OR = 2.639, 95%CI = 1.116–6.239, p = 0.027) in GR gene, but not for other polymorphisms (p > 0.05). The results of the present study suggest that GR genetic polymorphisms may play a major role in the efficacy of GCs in Chinese population with SLE.


Clinica Chimica Acta | 2010

Association of IL-1F7 gene with susceptibility to human leukocyte antigen-B27 positive Ankylosing spondylitis in Han Chinese population

Faming Pan; Fangfang Liao; Guo Xia; Rui Ge; Yang Mei; Xiaowu Tang; Heping Pan; Dong-Qing Ye; Yan-Feng Zou; Shengqian Xu; Jianhua Xu

Ankylosing spondylitis (AS) is one of the most common inflammatory arthritis, with an estimated prevalence of 0.1%–0.9%. Genetic factors have been strongly implicated in its etiology. Assessed by twin studies, the heritability of AS has been estimated to be 90% [1]. The disease has a strong genetic association with human leukocyte antigen-B27, however, only 1%–5% among those HLA-B27 positive populations developed AS, although most AS patients are HLA-B27 positive. Apparently, HLA-B27 alone does not account for the pattern of AS recurrence. Indeed, the contribution of HLA-B27 to the overall genetic predisposition has been estimated to be only 20%–30%. It has been proposed that non-major histocompatibility complex (non-MHC) genes contribute a major portion of genetic susceptibility to AS [2]. Genome-wide scans have demonstrated several areas of suggestive or significant linkage in non-MHC regions, including 1p, 1q, 2p, 3p, 2q, 5q, 9q, 10q, 11p, 11q, 16q, 17p, 17q and 19q [1,3,4]. Yet, candidate gene studies for non-MHC are limited. A genome-wide scan has identified that a region including interleukin-1 (IL-1) family gene cluster, which lies 123–126 cM from the p-telomere of chromosome 2, is linked to AS susceptibility [4]. Within a 360-kb region, IL-1 gene cluster includes IL-1α (IL1A), IL-1β (IL1B), IL-1F7, IL-1F9, IL-1F6, IL-1F8, IL-1F5, IL-1F10 and IL-1RN genes. This linkage finding was later confirmed by family-based association studies in western Canadian families population [5,6]. Based on these findings, Timms et al. concluded that the IL-1 gene cluster contains a susceptibility locus for AS [7]. Currently studies largely focus on IL-1A/B and IL-1RN genes [8,9]. It is noted that, across different populations, the association between AS and the polymorphisms of IL-1 gene is not identical, although similar [10,11]. Also, information regarding the association between IL-1 polymorphisms and AS is very limited in Chinese population. Therefore, we performed a case–control study on the association between AS and IL-1F7 gene single-marker polymorphism in concert with HLAB27 in Chinese population. We studied 181 unrelated AS patients (111 males and 70 females) with mean age of 26.3 y (SD=6.4 y), and 158 controls individuals (102 males and 56 females) with mean age of 28.2 y (SD=7.4 y). All the cases and controls are HLA-B27 positive. To reduce the influence of population stratification farthest, all the samples in our study are from local Anhuilanders, whose parents are also Anhuilanders. Permission was obtained from all individuals who were enrolled in this study. All patients were recruited from Department of Rheumatology, First Affiliated hospital, Anhui Medical University. All those control individuals had been screened by experienced rheumatism doctors before their blood samples were collected. Clinical diagnosis was carried out strictly according to the modified New York criteria [14]. Two IL-1F7 SNPs were selected from NCBI dbSNP (dbSNP home page).


Clinica Chimica Acta | 2015

Vitamin D in ankylosing spondylitis: review and meta-analysis.

Guoqi Cai; Li Wang; Dazhi Fan; Lihong Xin; Li Liu; Yanting Hu; Ning Ding; Shengqian Xu; Guo Xia; Xingzhong Jin; Jianhua Xu; Yan-Feng Zou; Faming Pan

BACKGROUND The role of vitamin D in ankylosing spondylitis (AS) is largely unknown. This paper aims to examine the association between serum vitamin D levels and susceptibility and disease activity of AS. METHODS We searched the relevant literatures in PubMed, Elsevier Science Direct, Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure (CNKI) and Wanfang (Chinese) Database published before June 2014. Eight independent case-control studies with a total of 533 AS patients and 478 matching controls were selected into this meta-analysis. Standard mean differences (SMDs) with 95% confidence intervals (CIs) were used to assess the levels of serum vitamin D, parathyroid hormone (PTH), serum calcium and alkaline phosphatase (ALP) in cases and controls, respectively. Correlation coefficients (CORs) have been performed to value the correlationship between vitamin D and disease activity (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) of AS patients. RESULTS Meta-analysis results suggested that vitamin D may play a protective role in AS (for total vitamin D: SMD=-0.71, P<0.001; for 25OHD: SMD=-0.66, P=0.002; for 1,25OHD: SMD=-0.72, P=0.19). Differences in PTH and serum calcium levels were not significant in AS (SMD=-0.10, P=0.67; SMD=0.12, P=0.17 respectively), while ALP was associated with AS susceptibility (SMD=0.20, P=0.04). The relationship between serum vitamin D levels and disease activity was statistically significant except for 25OHD versus (vs.) CRP or BASDAI (for CRP vs. 25OHD: COR=-0.22, P=0.08; for BASDAI vs. 25OHD: COR=-0.20, P=0.06, respectively). CONCLUSION The higher levels of serum vitamin D were associated with a decreased risk of AS, and showed an inverse relationship with AS activity.


International Journal of Immunogenetics | 2010

Association of SUMO4 M55V polymorphism with susceptibility to autoimmune and inflammatory diseases: a meta-analysis.

Yan-Feng Zou; Xiao-Liang Feng; J.-H. Tao; Ji-Min Zhu; Fan-Ming Pan; Hong Su; Dong-Qing Ye

The purpose of this study was to generate large‐scale evidence on whether SUMO4 M55V polymorphism is associated with autoimmune and inflammatory diseases using a meta‐analysis. We surveyed studies on the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases in PubMed. Meta‐analysis was performed for genotypes AG versus AA, GG versus AA, GG versus AA + AG, AG + GG versus AA and G allele versus A allele in a fixed/random effect model. We identified 16 studies (11 407 cases and 10 679 controls) using PubMed search. When all groups were pooled, we detected the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases (G versus A: OR = 1.11, 95%CI = 1.03–1.19, P = 0.005; AG + GG versus AA: OR = 1.17, 95%CI = 1.06–1.28, P = 0.001; GG versus AA + AG: OR = 1.07, 95%CI = 0.94–1.21, P = 0.29; GG versus AA: OR = 1.15, 95%CI = 1.00–1.34, P = 0.06; AG versus AA: OR = 1.15, 95%CI = 1.08–1.23, P < 0.0001). In subgroup analyses, we detected the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases in Asian population (G versus A: OR = 1.18, 95%CI = 1.08–1.28, P = 0.0001; AG + GG versus AA: OR = 1.30, 95%CI = 1.16–1.45, P < 0.00001; GG versus AA + AG: OR = 1.04, 95%CI = 0.78–1.37, P = 0.80; GG versus AA: OR = 1.20, 95%CI = 0.99–1.45, P = 0.07; AG versus AA: OR = 1.32, 95%CI = 1.18–1.49, P < 0.00001). But the association was not found in Caucasian population. Meanwhile, an association of SUMO4 M55V polymorphism with autoimmune diabetes was found (G versus A: OR = 1.18, 95%CI = 1.08–1.30, P = 0.0005; AG + GG versus AA: OR = 1.22, 95%CI = 1.13–1.32, P < 0.00001; GG versus AA + AG: OR = 1.15, 95%CI = 0.96–1.38, P = 0.13; GG versus AA: OR = 1.32, 95%CI = 1.08–1.60, P = 0.006; AG versus AA: OR = 1.23, 95%CI = 1.13–1.33, P < 0.00001). This meta‐analysis demonstrates the association of SUMO4 M55V polymorphism with autoimmune and inflammatory diseases, especially in Asian population.


Modern Rheumatology | 2015

Associations between ERAP1 polymorphisms and ankylosing spondylitis susceptibility: An updated meta-analysis

Guoqi Cai; Lihong Xin; Li Wang; Dazhi Fan; Li Liu; Yanting Hu; Ning Ding; Shengqian Xu; Guo Xia; Xingzhong Jin; Jianhua Xu; Yan-Feng Zou; Faming Pan

Abstract Objective. The relationship between the endoplasmic reticulum aminopeptidase 1 (ERAP1) polymorphisms and ankylosing spondylitis (AS) was inconsistent in the recent literatures, a meta-analysis was therefore performed. Methods. A total of 25 independent studies with 24,271 AS patients and 42,666 controls were included after searching electronic databases for studies published before June 2014. The pooled and individual odds ratios (ORs) with 95% confidence intervals (CIs) were presented to assess the associations between ERAP1 polymorphisms and AS in different ethnicities. Results. This meta-analysis includes 25 studies that investigate 8 single nucleotide polymorphisms (SNPs; rs17482078, rs30187, rs2287987, rs27044, rs26653, rs10050860, rs27037, and rs27434) in ERAP1 gene. Overall, six SNPs were associated with AS; two SNPs (rs27044 and rs26653) were not when all studies were pooled into the meta-analysis (rs27044 G vs. C, OR = 1.058, 95% CI = 0.827–1.354; rs26653 C vs. G, OR = 1.154, 95% CI = 0.937–1.422). In Caucasians, all the 8 SNPs were significantly associated with AS. But 5 SNPs (rs17482078, rs2287987, rs27044, rs26653, and rs10050860) did not show statistical association with the risk of AS in Asians. Conclusion. ERAP1 polymorphisms were associated with AS in Caucasians, but their association with AS in Asians needs further exploration.


Postgraduate Medicine | 2017

Increased plasma/serum levels of prolactin in systemic lupus erythematosus: a systematic review and meta-analysis.

Peng Wang; Tian-Tian Lv; Shi-Yang Guan; Hong-Miao Li; Rui-Xue Leng; Yan-Feng Zou; Hai-Feng Pan

ABSTRACT Background: Prolactin (PRL), a polypeptide hormone produced by the pituitary gland, is involved in the regulation of humoral and cell mediated immune responses. PRL levels have been investigated in several autoimmune diseases including systemic lupus erythematosus (SLE), however, yielded different and inconsistent results. This study aims to derive a more precise evaluation on plasma/serum PRL levels in SLE patients, as well as the potential influential factors. Methods: Studies published from 1 January 1987 to 31 December 2015 in English, which comparing plasma/serum PRL levels between SLE group and control group were searched in PubMed, EMBASE and The Cochrane Library databases. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effects or random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I2, publication bias was evaluated using a funnel plot and Egger’s linear regression test. Results: Five-hundred and forty-seven articles were obtained after searching databases, and 12 studies with 429 SLE patients and 326 controls were finally included. Meta-analysis revealed that, compared with the control group, the SLE group had significantly higher plasma/serum PRL levels (P < 0.001), with the SMD of 1.26 and 95%CI (0.70,1.82). Subgroup analyses showed that SLE patients from Asia and Europe had higher plasma/serum PRL levels. However, no significant change in plasma/serum PRL levels was observed in SLE patients from America (P > 0.05). Conclusions: Overall, our study suggests that SLE patients have higher plasma/serum PRL level, but with a regional difference.


Genetic Testing and Molecular Biomarkers | 2013

Association of XPC gene polymorphisms with susceptibility to prostate cancer: evidence from 3,936 subjects.

Yan-Feng Zou; Jin-Hui Tao; Qian-Ling Ye; Hai-Feng Pan; Faming Pan; Hong Su; Dong-Qing Ye

AIM Polymorphisms of xeroderma pigmentosum complementation group C (XPC) are thought to have significant effects on prostate cancer (PCa) risk. The aim of our study was to evaluate the impact of XPC gene polymorphisms on PCa risk by using a meta-analysis. METHODS Data were collected from the following electronic databases: PubMed, EMBASE, Elsevier Science Direct, Cochrane Library, and CNKI, with the last report up to April 30, 2013. Odds ratios with 95% confidence intervals were used to assess the strength of the association. RESULTS A total of five separate case-control studies (1966 cases and 1970 controls) were included in this meta-analysis. Meta-analysis was performed for the rs2228001 and PAT+/-polymorphisms. We did not detect a significant association between rs2228001 polymorphism and PCa (p>0.05). Similar results were found in stratification analyses by ethnicity and tumor stage. We detected a significant association of PAT+/-polymorphism with PCa (p<0.05). In stratification analysis, we did not detect a significant association of PAT+/-polymorphism with risk of bone metastasis in PCa patients (p>0.05). CONCLUSION These analyses suggest that XPC gene PAT+/-polymorphism, but not rs2228001, likely contributes to susceptibility to PCa.


Tissue Antigens | 2015

Association between DEFB103 gene copy number variation and ankylosing spondylitis: a case-control study.

Guoqi Cai; Qing Xia; Dazhi Fan; Xiaona Li; Ning Ding; Yanting Hu; Xiao Yang; Li Liu; Lihong Xin; Li Wang; Shengqian Xu; Jianhua Xu; Yan-Feng Zou; Changhai Ding; Faming Pan

In this brief communication, we investigate the role of DEFB103 gene copy number variation (CNV) in ankylosing spondylitis (AS) susceptibility. A total of 807 Chinese individuals including 406 AS patients and 401 controls were enrolled. The DEFB103 copy number was measured by two sets of probes to obtain a stable result in a custom-by-design Multiplex AccuCopy(™) kit (Genesky Biotechnologies Inc., Shanghai, China) based on a multiplex fluorescence competitive polymerase chain reaction (PCR) principle. The copy number of DEFB103 ranged from 2 to 6 in both AS patients and controls. Mann-Whitney U test and chi-squared test were performed to analyze the difference of DEFB103 copy number between AS patients and controls while no statistical difference has been found. We considered the copy number of DEFB103 gene may not associate with susceptibility to AS.


Journal of Clinical & Medical Genomics | 2015

Association of P2X7R Functional Expression and Gene Polymorphisms with Systemic Lupus Erythematosus

Jin-Hui Tao; Jiang-Ping Tang; Mei-Yun Wang; Hai-Feng Pan; Rui-Xue Leng; Yan-Feng Zou; Dong-Qing Ye; Xiang-Pei Li

Objective: To investigate P2X purinoceptor 7 (P2X7R) expression changes on peripheral blood mononuclear cell (PBMC) surfaces of systemic lupus erythematosus (SLE) patients as well as their association with serum cytokine levels and patients’ clinical features. In addition, the effects of different P2X7R single nucleotide polymorphisms (SNPs) on P2X7R expression and cytokine production were investigated. Method: Twenty-nine new-onset SLE patients and twenty-eight healthy controls were enrolled, while P2X7R expression levels of lymphocytes, CD4+ cells and CD19+ cells were analyzed by flow cytometry. Serum IL-1β, IL-6 and TNF-α levels were analyzed by ELISA and three P2X7R SNPs (1068G>A, 1096C>G and 1513A>C) were PCR genotyped in 14 SLE patients and 14 healthy controls. Results: P2X7R surface expression levels of lymphocytes, CD4+ and CD19+ cells from new-onset SLE patients were significantly higher than that of controls and significantly elevated on lymphocytes from patients with concurrent arthritis or leukopenia as well as on CD19+ cells of NP-SLE patients. Moreover, P2X7R expression levels on lymphocytes and CD19+ cells of SLE patients were positively correlated with serum TNF-α/IL-6 and TNF-α level, respectively. SLE patients with the P2X7R 1068GG genotype had significantly higher expression level ratios of TNF-α, IL-6 and IL-1β to P2X7R on lymphocytes compared to patients harboring the 1068GA genotype. Conclusion: P2X7R, as an important cell surface regulator of several key cytokines, is involved in the pathogenesis of SLE and also associated with organ injuries like arthritis, leukopenia and neuropsychiatric damage. P2X7R 1068GG maybe a SLE susceptibility genotype since it enhances cytokine secretion in SLE patients.


Tissue Antigens | 2011

Association of NFKB1 -94ins/delATTG promoter polymorphism with susceptibility to autoimmune and inflammatory diseases: a meta-analysis.

Yan-Feng Zou; Fang Wang; Xiao-Liang Feng; Jin-Hui Tao; Ji-Min Zhu; Fan-Ming Pan; Hong Su

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Dong-Qing Ye

Anhui Medical University

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Faming Pan

Anhui Medical University

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Hai-Feng Pan

Anhui Medical University

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Jin-Hui Tao

Anhui Medical University

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Jianhua Xu

Anhui Medical University

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Hong Su

Anhui Medical University

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Shengqian Xu

Anhui Medical University

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Dazhi Fan

Anhui Medical University

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Guo Xia

Anhui Medical University

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Guoqi Cai

Anhui Medical University

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