Fei Sun

Peking Union Medical College Hospital, Peping, Beijing, China

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Publications (11)79.84 Total impact

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    ABSTRACT: AimThe vasculitis diseases granulomatosis with polyangiitis (GPA) and microscopic polyangitis (MPA) are the two major forms of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). A recent genome-wide association study has shown that the genes HLA-DPB1 and HLA-DQ conferred susceptibility to GPA and MPA, respectively. We investigated the linkage between putative AAV-related genes (HLA-DPB1, ARHGAP18, CD226, CTLA-4, MOSPD2 and PRTN3) and AAV in a Han Chinese population.MethodA Sequenom MassAarray system (iPLEX assay, Sequenom, San Diego, CA, USA) was used to genotype single nucleotide polymorphisms (SNPs) in 176 Han Chinese patients with AAV (100 with GPA, 76 with MPA) and 485 ethnically matched healthy controls.ResultThe frequency of the rs3117242 variant T allele (HLA-DPB1) was significantly higher in GPA patients than in the controls (68.0% compared with 50.4%, OR = 2.09, 95% CI: 1.51–2.88, Bonferroni corrected P-value [Pc] = 6.24E-5), but was not significantly different between MPA patients and controls (Pc = 0.14). The same results were obtained via genotype distribution and logistic regression analysis based on three genetic models. The allele and genotype distributions of the other polymorphisms were not significantly associated with AAV patients as a whole or GPA or MPA patients considered separately.Conclusion The rs3117242 of HLA-DPB1 could be considered a genetic risk factor for GPA in Chinese Han people. These findings provide further insights and clues into the etiology of GPA and MPA.
    International Journal of Rheumatic Diseases 05/2015; DOI:10.1111/1756-185X.12561 · 1.77 Impact Factor
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    Dataset: ng.898
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    ABSTRACT: Background Single-nucleotide polymorphisms (SNPs) in the TNFAIP3, IFIH1, and IRF5 genes have been associated with several auto-inflammation diseases, while the susceptibility between these genes and idiopathic inflammatory myopathies (IIMs) were not reported. This study aimed to investigate whether TNFAIP3, IFIH1, and IRF5 gene polymorphisms confer susceptibility for the IIMs in Chinese Han population. Methods A large case–control study of Chinese subjects with polymyositis (PM) (n = 298) and dermatomyositis (DM) (n = 530) was accomplished. 968 healthy and ethnically matched controls were available for comparison. Six SNPs in the TNFAIP3 region (rs2230926 and rs5029939), the IFIH1 gene (rs1990760 and rs3747517) and the IRF5 region (rs4728142 and rs729302) were assessed and genotyped using the Sequenom MassArray iPLEX platform. Results Our study indicated a strong allele association was observed in PM/DM and PM patients for rs2230926 (OR: 1.61, 95%CI: 1.20–2.16, Pc = 7.5×10−3; OR: 1.88, 95%CI: 1.30–2.74, Pc = 4.0×10−3, respectively) and rs5029939 (OR: 1.64, 95%CI: 1.21–2.21, Pc = 6.0×10−3; OR: 1.88, 95%CI: 1.28–2.76, Pc = 5.5×10−3,respectively). And rs2230926 and rs5029939 were significantly associated with interstitial lung disease (ILD) in PM/DM and PM patients (Pc = 0.04 and Pc = 0.016; Pc = 0.02 and Pc = 0.03, respectively). In addition, rs4728142 allele and genotype had significant association with PM/DM patients (Pc = 0.026 and Pc = 0.048, respectively). Further analysis with three logistic regression genetic models revealed statistically significant difference in the genotypic distribution in the PM/DM, PM or DM patients when the additive and dominant models were used. Conclusions This was the first study to reveal TNFAIP3 and IRF5 polymorphisms were associated with PM/DM patients or these patients with ILD, indicating that TNFAIP3 and IRF5 might be the susceptibility gene for PM/DM patients in Chinese Han population.
    PLoS ONE 10/2014; 9(10):e110044. DOI:10.1371/journal.pone.0110044 · 3.53 Impact Factor
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    ABSTRACT: Objectives. Our study was designed to evaluate the association of single nucleotide polymorphisms (SNPs) of the TLR2 gene with antineutrophil cytoplasmic autoantibodies (ANCAs)-associated vasculitides (AAV) in the northern Han Chinese population. Methods. The TLR2 SNPs rs1898830, rs11938228, rs3804099, rs3804100, and rs7656411 were analyzed in 195 AAV patients [granulomatosis with polyangiitis (GPA), n = 100; microscopic polyangiitis (MPA), n = 76; eosinophilic granulomatosis with polyangiitis (EGPA), n = 19] and 501 ethnically and geographically matched healthy controls. Genetic association analysis was carried out using PLINK (version 1.07). For multiple comparisons, a Bonferroni adjustment was conducted (pc = p*n, where n was the number of tested SNPs). Results. The overall frequencies of alleles and genotypes of TLR2 polymorphisms did not differ significantly between AAV patients and controls. The C allele of rs3804100 and the haplotype (C-C) formed by rs3804100 and rs3804099, however, were over-represented in the MPA patient group (pc = 0.018, pc = 0.016, respectively). Moreover, the frequencies of the C allele of both rs3804100 and rs3804099 were higher in the anti-MPO ANCA positive subgroup vs. healthy controls (pc = 0.003, pc = 0.013, respectively). Conclusions. We conclude that rs3804100 of TLR2 predisposes to MPA in northern Han Chinese. Future studies with larger sample sizes in the northern Han Chinese and other populations are required to extend and verify our current findings.
    Modern Rheumatology 09/2014; 25(2):1-6. DOI:10.3109/14397595.2014.950034 · 2.21 Impact Factor
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    ABSTRACT: Behçet's disease (BD) is a rare, chronic, relapsing, systemic, immune-mediated vasculitis and the etiology remains to be defined. This study investigated single-nucleotide polymorphisms (SNP) of tyrosine-protein phosphatase non-receptor type 2 (PTPN2) and inducible T-cell co-stimulator-ligand gene (ICOSLG) in Chinese Han BD patients and healthy controls because SNPs of these two genes are associated with risk of developing other auto-inflammation diseases. A total of 407 BD patients and 679 ethnically matched healthy controls were recruited for genotyping of PTPN2 rs1893217, rs2542151, rs2847297 and rs7234029 SNPs and ICOSLG rs2838519 and rs762421 SNPs using a Sequenom MassArray system. PTPN2 rs1893217 was associated with risk of developing BD (χ2=10.01, pc=0.040), while the PTPN2 rs2542151 genotype had a weak association in basic genotype analysis (χ2=7.49, p=0.024), but it could not withstand the strongest Bonferroni correction (pc=0.14). In contrast, PTPN2 rs2847297 and rs7234029 and ICOSLG rs2838519 and rs762421 did not correlate with BD risk. Moreover, logistic analysis with the additive, dominant and recessive genetic models did not reveal any statistical difference between BD cases and controls (pc>0.05). In addition, associations were observed between the two SNPs (rs1893217, rs2542151) and the patients with gastrointestinal involvement (pc=0.027, pc=0.032, respectively). PTPN2 variant rs1893217 was associated with risk of BD development in a Han Chinese population. Further study will confirm this finding and investigate the role of PTPN2 in development of BD.
    Clinical and experimental rheumatology 01/2014; · 2.97 Impact Factor
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    ABSTRACT: IL-10 is a potent anti-inflammatory cytokine that plays important roles in the pathogenesis of Behçet's disease (BD). Two genome-wide association studies have identified IL10 as a potential risk factor for BD. Here, we investigated the association between IL10 polymorphisms and BD in Chinese Han. 407 BD patients and 679 healthy controls were enrolled, and genotyped by Sequenom MassArray system (Sequenom iPLEX assay, San Diego, CA). The frequency of risk allele of rs1800871 was notably higher in BD patients than in controls (71.9% vs. 66.2%, OR: 1.30, 95% CI: 1.08 - 1.58, pc = 0.024). Similarly, rs1518111, which showed strong linkage disequilibrium (r(2) = 1) with allele rs1800871, was also associated with BD (pc = 0.026). Rs3021094 was in association with BD in a dominant model (pc = 0.035), and the haplotype (GACC) formed by rs1518111, rs3021094, rs3790622, and rs1800871 was associated with BD (pc = 0.023). Results obtained from meta-analysis combined with our data showed that rs1800871 and rs1518111 were associated with BD. IL10 may be the susceptibility gene for BD in Chinese Han population.
    Human immunology 11/2013; 75(3). DOI:10.1016/j.humimm.2013.11.009 · 2.28 Impact Factor
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    ABSTRACT: Primary Sjögren's syndrome is one of the most common autoimmune diseases. So far, genetic studies of Sjögren's syndrome have relied mostly on candidate gene approaches. To identify new genetic susceptibility loci for primary Sjögren's syndrome, we performed a three-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 556,134 autosomal SNPs in 542 cases and 1,050 controls. We then validated promising associations in 2 replication stages comprising 1,303 cases and 2,727 controls. The combined analysis identified GTF2I at 7q11.23 (rs117026326: Pcombined = 1.31 × 10(-53), combined odds ratio (ORcombined) = 2.20) as a new susceptibility locus for primary Sjögren's syndrome. Our analysis also confirmed previously reported associations in Europeans in the regions of STAT4, TNFAIP3 and the major histocompatibility complex (MHC). Fine mapping of the region around GTF2I showed that rs117026326 in GTF2I had the most significant association, with associated SNPs extending from GTF2I to GTF2IRD1-GTF2I.
    Nature Genetics 10/2013; DOI:10.1038/ng.2779 · 29.65 Impact Factor
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    ABSTRACT: Primary Sjögren's syndrome (pSS) is an autoimmune disease with a complex genetic background. Single nucleotide polymorphisms (SNPs) in the BANK1 and FAM167A-BLK genes have been associated with multiple autoimmune diseases. In this study, we investigated whether SNPs in the BANK1 (rs4522865, rs17266594, and rs10516487) and in the FAM167A-BLK region (rs2736340, rs13277113) could be associated with pSS in Chinese Han. Blood DNA was extracted from 540 patients with pSS and 577 healthy controls, and genotyped using the Sequenom MassArray system. There was no significant association between the polymorphisms of BANK1 and pSS. However, the frequency of Pss patients with the T allele (rs2736340) and A allele (rs13277113) of the FAM167A-BLK region was higher than that in the controls (p=0.034; p=0.026 respectively). Genotype and haplotype frequencies of these two SNPs (rs2736340 and rs13277113) between the patients and healthy controls were also significantly different. In addition, associations were observed between the two SNPs and the patients negative for anti-LA/SSB antibodies (p=0.036 and p=0.031 respectively). There was no epistatic interaction between the SNPs in the BANK1 and FAM167A-BLK region. Our results indicated that the SNPs (rs2736340, rs13277113) of the FAM167A-BLK region, but not the BANK1 SNPs (rs4522865, rs17266594, and rs10516487), were associated with the development of pSS in Han Chinese.
    Clinical and experimental rheumatology 07/2013; · 2.97 Impact Factor
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    ABSTRACT: Single-nucleotide polymorphisms (SNPs) in the TNFSF4, TNFAIP3 and FAM167A-BLK genes have been associated with several autoimmune diseases. Associations of TNFSF4 and FAM167A-BLK with primary Sjogren's syndrome (pSS) have also been described in a Caucasian population. However, it remains unknown whether polymorphisms of TNFSF4, TNFAIP3 and FAM167A-BLK are associated with pSS in Han Chinese. This study aimed to determine whether SNPs in TNFSF4, TNFAIP3 or FAM167A-BLK genetically predispose a Chinese Han population to pSS. Ten SNPs in the TNFSF4 region (rs1234315, rs2205960, rs844648 and rs704840), the TNFAIP3 gene (rs5029939 and rs2230926) and the FAM167A-BLK region (rs7812879, rs2254546, rs2618479 and rs2248932) were genotyped in a cohort of 555 pSS patients and 597 healthy controls, by using the Sequenom MassArray system. Weak associations were observed when the SNPs in TNFSF4 (rs2205960, rs844648 and rs704840) and FAM167A-BLK (rs7812879, rs2254546 and rs2618479) were directly analyzed or analyzed under dominant model between pSS and controls (all P<0.05). However, when Bonferroni correction was applied to the multiple comparisons, all of the associations vanished, except for rs7812879 (Pa=0.045). The frequencies of alleles, genotypes and haplotypes of TNFAIP3 SNPs and rs2248932 of FAM167A-BLK were not significantly different between the pSS patients and controls. No epistatic interactions were found to exist between the SNPs examined. Unlike the SNPs in TNFAIP3 and TNFSF4, rs7812879 in FAM167A-BLK imparts susceptibility to pSS in a Han Chinese population. The differential genetic risk profiles from other autoimmune diseases may indicate differential molecular mechanisms underlying pSS pathogenesis in this group.Journal of Human Genetics advance online publication, 2 May 2013; doi:10.1038/jhg.2013.26.
    Journal of Human Genetics 05/2013; DOI:10.1038/jhg.2013.26 · 2.53 Impact Factor
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    ABSTRACT: Graves' disease is a common autoimmune disorder characterized by thyroid stimulating hormone receptor autoantibodies (TRAb) and hyperthyroidism. To investigate the genetic architecture of Graves' disease, we conducted a genome-wide association study in 1,536 individuals with Graves' disease (cases) and 1,516 controls. We further evaluated a group of associated SNPs in a second set of 3,994 cases and 3,510 controls. We confirmed four previously reported loci (in the major histocompatibility complex, TSHR, CTLA4 and FCRL3) and identified two new susceptibility loci (the RNASET2-FGFR1OP-CCR6 region at 6q27 (P(combined) = 6.85 × 10(-10) for rs9355610) and an intergenic region at 4p14 (P(combined) = 1.08 × 10(-13) for rs6832151)). These newly associated SNPs were correlated with the expression levels of RNASET2 at 6q27, of CHRNA9 and of a previously uncharacterized gene at 4p14, respectively. Moreover, we identified strong associations of TSHR and major histocompatibility complex class II variants with persistently TRAb-positive Graves' disease.
    Nature Genetics 08/2011; 43(9):897-901. DOI:10.1038/ng.898 · 29.65 Impact Factor
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    ABSTRACT: Obesity is frequently associated with malfunctions of the hypothalamus-pituitary-adrenal (HPA) axis and hyperaldosteronism, but the mechanism underlying this association remains unclear. Since the adrenal glands are embedded in adipose tissue, direct cross-talk between adipose tissue and the adrenal gland has been proposed. A previous study found that adiponectin receptor mRNA was expressed in human adrenal glands and aldosterone-producing adenoma (APA). However, the expression of adiponectin receptors in adrenal glands has not been confirmed at the protein level or in other species. Furthermore, it is unclear whether adiponectin receptors expressed in adrenal cells are functional. We found, for the first time, that adiponectin receptor (AdipoR1 and AdipoR2) mRNA and protein were expressed in mouse adrenal and adrenocortical Y-1 cells. However, adiponectin itself was not expressed in mouse adrenal or Y-1 cells. Furthermore, adiponectin acutely reduced basal levels of corticosterone and aldosterone secretion. ACTH-induced steroid secretion was also inhibited by adiponectin, and this was accompanied by a parallel change in the expression of the key genes involved in steroidogenesis. These findings indicate that adiponectin may take part in the modulation of steroidogenesis. Thus, adiponectin is likely to have physiological and/or pathophysiological significance as an endocrine regulator of adrenocortical function.
    Biochemical and Biophysical Research Communications 10/2009; 390(4):1208-13. DOI:10.1016/j.bbrc.2009.10.122 · 2.28 Impact Factor