Aize Kijlstra

Maastricht Universitair Medisch Centrum, Maestricht, Limburg, Netherlands

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Publications (196)488.45 Total impact

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    ABSTRACT: Considering the phenotypical consequences and association of C4 copy number variation (CNV) with various autoimmune diseases, we aimed to examine C4 CNVs for 1027 patients with Vogt-Koyanagi-Harada (VKH) syndrome and 2083 controls.
    The British journal of ophthalmology. 09/2014;
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    ABSTRACT: To identify new genetic risk factors for Vogt-Koyanagi-Harada (VKH) syndrome, we conducted a genome-wide association study of 2,208,258 SNPs in 774 cases and 2,009 controls with follow-up in a collection of 415 cases and 2,006 controls and a further collection of 349 cases and 1,588 controls from a Han Chinese population. We identified three loci associated with VKH syndrome susceptibility (IL23R-C1orf141, rs117633859, Pcombined = 3.42 × 10(-21), odds ratio (OR) = 1.82; ADO-ZNF365-EGR2, rs442309, Pcombined = 2.97 × 10(-11), OR = 1.37; and HLA-DRB1/DQA1, rs3021304, Pcombined = 1.26 × 10(-118), OR = 2.97). The five non-HLA genes were all expressed in human iris tissue. IL23R was also expressed in the ciliary body, and EGR2 was expressed in the ciliary body and choroid. The risk G allele of rs117633859 in the promoter region of IL23R exhibited low transcriptional activation in a cell-based reporter assay and was associated with diminished IL23R mRNA expression in human peripheral blood mononuclear cells.
    Nature Genetics 08/2014; 46(9):1007-11. · 35.21 Impact Factor
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    ABSTRACT: PurposeThe purpose of this study was to investigate the effect of lutein on systemic complement activation in elderly individuals.Methods Seventy patients with signs of early age-related macular degeneration (AMD) were included in this study. All subjects were randomly assigned to receive a 10 mg daily dose of lutein or a placebo for a time period of 1 year. EDTA blood was collected before and at various time-points during the study (0, 4, 8 and 12 months). The plasma level of the soluble complement membrane attack complex sC5b-9 was measured by ELISA.ResultsWe found a significant 1.1 ng/ml monthly decrease in the plasma sC5b-9 concentration in the lutein group (p < 0.001), resulting in a decrease from 60.3 ng/ml at baseline to 46.3 ng/ml at 12 months. For the placebo group, we found a significant 0.6 ng/ml monthly increase in plasma sC5b-9 concentration (p = 0.001), resulting in an increase from 51.6 ng/ml at baseline to 58.4 ng/ml at 12 months.Conclusions Lutein supplementation inhibits the systemic activation of the complement system, which provides further functional evidence for the reported beneficial effects of this carotenoid in the management of AMD.
    Acta ophthalmologica 08/2014; · 2.44 Impact Factor
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    L Wu, H Wen, Y Zhou, H Yu, Y Liu, L Bai, A Kijlstra, P Yang
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    ABSTRACT: Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome are two intraocular inflammatory diseases that are caused by an aberrant T lymphocyte response. Th17 cells, mainly producing the cytokine IL-17, and Th1 cells, characterized by the production of the index cytokine IFN-γ, are the CD4+ T lymphocyte subsets implicated in the pathogenesis of both BD and VKH. Suppressing the excessive response of these Th17 and Th1 cells has been reported to be an effective therapeutic approach to treat these patients and continuous efforts are being undertaken to find new methods to modulate the function of these cells. Evidence is emerging that the Liver X receptor (LXR) is an important regulator of inflammatory and immune responses and the study reported here was designed to investigate the role of LXR activation in BD and VKH. Here we demonstrate that the frequency of Th17 and Th1 cells along with the relevant cytokines IL-17, IFN-γ and corresponding transcriptional factors RORC, T-bet were all decreased following LXR activation by the agonist GW3965. LXR controlled the expression of inflammatory cytokines through an effect on NF-kappa B (NFκb) phosphorylation. Data from our study provide evidence for an association between a decreased LXR expression and disease activity in both BD and VKH, due to the fact that a lower LXR activation may result in an enhanced Th1 and Th17 immune response. Our study suggests that enhancing LXR activation may offer a potential therapeutic approach targeting aberrant immune responses by inhibiting Th1 and Th17 cell responses.
    Current Molecular Medicine 07/2014; 14(6):712-22. · 4.20 Impact Factor
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    ABSTRACT: Dietary lutein intake is postulated to interfere with the development of age-related macular degeneration (AMD). Because egg yolk-derived lutein has a high bioavailability, long-term consumption of lutein-enriched eggs might be effective in preventing AMD development, but alternatively might increase cardiovascular disease risk. Here, we report the effect of 1-y daily consumption of a buttermilk drink containing 1.5 lutein-rich egg yolks on serum lipid, lipoprotein, and plasma lutein concentrations. Additionally, subgroups that could potentially benefit most from the intervention were identified. Men and women who had early signs of AMD in at least 1 eye, but were otherwise healthy, participated in a 1-y randomized, placebo-controlled parallel intervention trial. At the start of the study, 101 participants were included: 52 in the experimental (Egg) group and 49 in the control (Con) group. Final analyses were performed with 45 participants in the Egg group and 43 participants in the Con group. As expected, the increase in plasma lutein concentrations in the Egg group was 83% higher than that in the Con group (P < 0.001). Changes in serum total cholesterol and HDL and LDL cholesterol, as well as the ratio of total cholesterol to HDL cholesterol, were not different between the 2 groups. Interestingly, participants classified as cholesterol absorbers had higher serum HDL cholesterol concentrations than participants classified as cholesterol synthesizers or participants with average campesterol-to-lathosterol ratios (P < 0.05) at baseline. In addition, cholesterol absorbers had a 229% higher increase in plasma lutein concentrations than participants who were classified as having an average campesterol-to-lathosterol ratio (P < 0.05) upon consumption of the lutein-enriched egg yolk drink. Moreover, the change in serum HDL cholesterol upon consumption was significantly different between these 3 groups (P < 0.05). We suggest that cholesterol absorbers particularly might benefit from the lutein-enriched buttermilk drink. This study was registered at clinicaltrials.gov as NCT00902408.
    The Journal of nutrition. 07/2014;
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    ABSTRACT: Instruction: Interleukin (IL)-27 is an important regulator of the pro-inflammatory T cell response. In this study, we investigated its role in the pathogenesis of Behcet's disease (BD).
    Arthritis research & therapy. 05/2014; 16(3):R117.
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    ABSTRACT: Protein tyrosine phosphatase non-receptor 22 (PTPN22) is a key negative regulator of T lymphocytes and has emerged as an important candidate susceptibility factor for a number of immune-related diseases. This study aimed to examine the predisposition of PTPN22 SNPs to Vogt-Koyanagi-Harada (VKH) syndrome and acute anterior uveitis (AAU) associated with ankylosing spondylitis (AS). A total of 1005 VKH syndrome, 302 AAU+AS+ patients and 2010 normal controls among the Chinese Han population were enrolled in the study. Genotyping, PTPN22 expression, cell proliferation, cytokine production and cell activation were examined by PCR-RFLP, Real-time PCR, CCK8, ELISA and Flow cytometry. The results showed significantly increased frequencies of the rs2488457 CC genotype and C allele but a decreased frequency of the GG genotype in VKH syndrome patients (PBonferroni correction (Pc) = 3.47×10-7, OR = 1.54; Pc = 3.83×10-8, OR = 1.40; Pc = 6.35×10-4, OR = 0.62; respectively). No significant association of the tested SNPs with AAU+AS+ patients was observed. Functional studies showed a decreased PTPN22 expression, impaired cell proliferation and lower production of IL-10 in rs2488457 CC cases compared to GG cases (Pc = 0.009, Pc = 0.015 and Pc = 0.048 respectively). No significant association was observed concerning T cell activation and rs2488457 genotype. The study showed that a functional variant of PTPN22 confers risk for VKH syndrome but not for AAU+AS+ in a Chinese Han population, which may be due to a modulation of the PTPN22 expression, PBMC proliferation and IL-10 production.
    PLoS ONE 05/2014; 9(5):e96943. · 3.53 Impact Factor
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    ABSTRACT: Previous studies have identified miR-182, miR-27a, FoxO1, and IL2RA as regulatory factors for Treg cell development and function. In order to investigate the association of miR-182, miR-27a, FoxO1, and IL2RA gene polymorphisms with Behçet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population, a two-stage association study was performed in 820 BD, 900 VKH patients, and 1,800 controls using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. In the first stage study, association analysis of 10 single nucleotide polymorphisms (SNPs) was performed in 400 BD, 400 VKH patients, and 600 controls. The results showed significantly decreased frequencies of the miR-182/rs76481776 CC genotype and C allele in BD (P = 3.36 × 10(-4), OR = 0.55; P = 4.74 × 10(-4), OR = 0.59) and VKH patients (P = 1.11 × 10(-4), OR = 0.53; P = 1.26 × 10(-4), OR = 0.56). No significant association of the other nine SNPs with BD or VKH was observed. In the second stage study, association analysis of miR-182/rs76481776 was performed in 420 BD, 500 VKH patients, and 1,200 controls. The second stage and combined studies confirmed the association of miR-182/rs76481776 with BD (CC genotype: P = 3.25 × 10(-7), OR = 0.58; C allele: P = 1.81 × 10(-7), OR = 0.60) and VKH (CC genotype: P = 7.89 × 10(-8), OR = 0.57; C allele: P = 2.52 × 10(-8), OR = 0.59). Real-time PCR analysis showed a significantly increased expression of miR-182 in TT/CT cases compared to CC cases in anti-CD3/CD28 antibodies-stimulated CD4(+) T cells (P = 2.1 × 10(-2)). In conclusion, this study suggests that miR-182, but not miR-27a, FoxO1, and IL2RA, contributes to the genetic susceptibility of BD and VKH. MiR-182 contributes to genetic susceptibility of BD and VKH. No significant association of miR-27a, FoxO1, and IL2RA with BD or VKH was observed. Significantly increased expression of miR-182 in TT/CT cases compared to CC cases was observed.
    Journal of Molecular Medicine 05/2014; 92(9):961-7. · 4.77 Impact Factor
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    ABSTRACT: AhR is well known for mediating the toxic effects of dioxin containing pollutants but has also been shown to be involved in the natural regulation of the immune response. In this study, we investigated the effect of AhR activation by its endogenous ligands 6-formylindolo[3,2-b]carbazole (FICZ), and 2-(1′Hindole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) on the differentiation, maturation and function of monocyte-derived DCs in Behcet's disease (BD) patients. Here, we showed that AhR activation by FICZ and ITE downregulated the expression of co-stimulatory molecules including HLA-DR, CD80 and CD86, while it had no effect on the expression of CD83 and CD40 on DCs derived from BD patients and normal controls. LPS-treated DCs from active BD patients showed a higher level of IL-1β, IL-6, IL-23 and TNF-α production. FICZ or ITE significantly inhibited the production of IL-1β, IL-6, IL-23 and TNF-α, but induced IL-10 production by DCs derived from active BD patients and normal controls. FICZ or ITE-treated DCs significantly inhibited the Th17 and Th1 cell response. Activation of AhR either by FICZ or ITE inhibits DC differentiation, maturation and function. Further studies are needed to investigate whether manipulation of the AhR pathway may be used to treat BD or other autoimmune diseases.
    Clinical & Experimental Immunology 04/2014; · 3.41 Impact Factor
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    ABSTRACT: Objective. Behçet's disease (BD) is a refractory inflammatory disorder with unknown causes. Since the Notch pathway is critically involved in the immune response, the present study was undertaken to investigate the role of this pathway in BD.Methods. Hes-1, Notch 1-4, Jagged-1, DLL-1 and DLL-4 expression, frequency of IFN-γ and IL-17 expressing Th cells, Notch intracellular domain (NICD), phosphorylation of signal transducer and activator of transcription 3 (STAT3) and the production of IFN-γ and IL-17 were examined by real-time PCR, flow cytometry and ELISA. Notch blockade was performed using the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT). Transfection with miR-23b mimics and inhibitor was used to examine the effect of miR-23b on Notch pathway activation.Results. Active BD patients showed an increased activation of the Notch pathway in association with a higher Th17 response. Notch blockade preferentially inhibited Th17 responses. The effect of Notch blockade on the Th17 response was associated with a lower level of STAT3 phosphorylation. miR-23b was significantly decreased in CD4(+) T cells from active BD patients. CD4(+) T cells transfected with miR-23b showed a reduced expression of NICD and a reduced frequency of IL-17- and IFN-γ-expressing T cells.Conclusion. The present study suggests that an increased activation of the Notch pathway may contribute to the pathogenesis of BD. Decreased expression of miR-23b may be involved in activation of the Notch pathway in BD. Manipulation of the Notch pathway may offer a novel therapeutic approach for BD.
    Rheumatology (Oxford, England) 01/2014; 53(5):810-20. · 4.24 Impact Factor
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    ABSTRACT: To investigate the associations of single nucleotide polymorphisms (SNPs) of three genes (IL-12B, IL-12Rβ1 and IL-12Rβ2) in Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population.
    PLoS ONE 01/2014; 9(5):e98373. · 3.53 Impact Factor
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    ABSTRACT: TRAF5 and TRAF3IP2 have been reported to be associated with several autoimmune diseases. Behçet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome are two autoimmune uveitis entities whereby both genetic and environmental factors are thought to be involved. The role of TRAF5 and TRAF3IP2 in BD and VKH has not yet been reported and was therefore the subject of this study. The study included 789 BD patients, 940 VKH patients and 1601 healthy unrelated individuals. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan® SNP Genotyping Assay. Real-Time PCR was used to detect mRNA expression from PBMCs obtained from healthy controls with (n = 22) or without (n = 79) stimulation. Levels of TNF-α, IL-6 and IL-8 in culture supernatants were measured by ELISA (n = 22). Three SNPs (rs6540679, rs12569232, rs10863888) of TRAF5 and rs13210247 of TRAF3IP2 were significantly associated with Behçet's disease and VKH syndrome (corrected P values ranging from 9.45×10(-12) to 0.027). TRAF3IP2 rs33980500 and rs13190932 were not polymorphic in Han Chinese. Following stimulation by lipopolysaccharide (LPS), carriers of the GG genotype of rs6540679/TRAF5 had a higher TRAF5 mRNA expression (p = 0.004) and an increased TNF-α (p = 0.0052) and IL-6 (p = 0.0014) level compared with AA and AG genotype carriers. This study provides evidence that TRAF5 and TRAF3IP2 genes are involved in the development of BD and VKH syndrome. Functional research suggested that TRAF5 gene polymorphisms may regulate TRAF5 expression and downstream inflammatory cytokines such as TNF-α and IL-6.
    PLoS ONE 01/2014; 9(1):e84214. · 3.53 Impact Factor
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    ABSTRACT: MicroRNA-146a (miR-146a) was a key negative regulator of autoimmunity. V-Ets oncogene homolog 1 (Ets-1) was demonstrated to bind to the miR-146a promoter region and markedly affects miR-146a promoter activity. This study aimed to investigate the association of miR-146a and Ets-1 gene polymorphisms with pediatric uveitis in a Han Chinese population. A total of 520 patients and 1204 healthy controls were included in the present study. Five single-nucleotide polymorphisms (SNPs), miR-146a/rs2910164, miR-146a/rs57095329, miR-146a/rs6864584, ets-1/rs1128334 and ets-1/rs10893872 were genotyped using a polymerase chain reaction-restriction fragment length polymorphism assay. The expression of Ets-1 in peripheral blood mononuclear cells from genotyped healthy controls was tested by real-time PCR. Two SNPs (rs2910164 and rs10893872) were associated with pediatric uveitis in this study. The frequencies of the rs2910164 GG genotype and G allele were significantly increased (Pc = 3.11×10-4; Pc = 2.75×10-6) while the CC genotype and C allele were significantly decreased (Pc = 0.001; Pc = 2.75×10-6) in patients compared with normal controls. The frequencies of the rs10893872 CC genotype and C allele were significantly increased (Pc = 3.89×10-4; Pc = 0.01) while the CT genotype and T allele were significantly decreased (Pc = 0.004; Pc = 0.01) in patients compared with normal controls. The SNP rs2910164 GG genotype and G/C allele were also associated with the presence of microvascular leakage as detected by fundus fluorescein angiography in pediatric uveitis (Pc = 0.01; Pc = 0.005, respectively). Ets-1 expression in rs10893872 CC carriers was significantly higher than in CT and TT individuals (Pc = 0.013). There was no association of the other three SNPs with pediatric uveitis. This study shows that miR-146a and Ets-1 are both associated with pediatric uveitis in Han Chinese. SNP rs10893872 may affect the genetic predisposition to pediatric uveitis by modulating expression of Ets-1.
    PLoS ONE 01/2014; 9(3):e91199. · 3.53 Impact Factor
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    ABSTRACT: Increasing evidence suggests a beneficial effect of lutein and zeaxanthin on the progression of age-related macular degeneration. The aim of this study was to investigate the effect of lutein or zeaxanthin enriched eggs or a lutein enriched egg-yolk based buttermilk beverage on serum lutein and zeaxanthin concentrations and macular pigment levels. Naturally enriched eggs were made by increasing the levels of the xanthophylls lutein and zeaxanthin in the feed given to laying hens. One hundred healthy volunteers were recruited and randomized into 5 groups for 90 days. Group one added one normal egg to their daily diet and group two received a lutein enriched egg-yolk based beverage. Group three added one lutein enriched egg and group four one zeaxanthin enriched egg to their diet. Group five was the control group and individuals in this group did not modify their daily diet. Serum lutein and zeaxanthin concentrations and macular pigment densities were obtained at baseline, day 45 and day 90. Macular pigment density was measured by heterochromatic flicker photometry. Serum lutein concentration in the lutein enriched egg and egg yolk-based beverage groups increased significantly (p<0.001, 76% and 77%). A strong increase in the serum zeaxanthin concentration was observed in individuals receiving zeaxanthin enriched eggs (P< 0.001, 430%). No changes were observed in macular pigment density in the various groups tested. The results indicate that daily consumption of lutein or zeaxanthin enriched egg yolks as well as an egg yolk-based beverage show increases in serum lutein and zeaxanthin levels that are comparable with a daily use of 5 mg supplements. ClinicalTrials.gov NCT00527553.
    PLoS ONE 01/2014; 9(3):e92659. · 3.53 Impact Factor
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    ABSTRACT: The aim of the study was to investigate the association of TNFα-induced protein 3 interacting with protein 1 (TNIP1) gene polymorphisms with Vogt-Koyanagi-Harada (VKH) syndrome and Behcet's disease (BD) in a Han Chinese population. A total of 656 BD patients, 961 VKH syndrome patients and 1534 healthy controls were included in this two-stage case control study. Seven SNPs, including rs17728338, rs7708392, rs10036748, rs3762999, rs999556, rs4958881 and rs3792783, belonging to TNIP1 were genotyped and analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The data were analyzed by using the χ2 or Fisher's exact test and corrected for multiple comparisons by the Bonferroni method. A significantly increased frequency of the GG genotype and a decreased frequency of the AG genotype of rs17728338 were found in VKH patients (Pc = 0.038 OR = 1.934, 95% CI = 1.438∼2.601). No significant difference was noted in allele or genotype frequencies of rs7708392, rs10036748, rs3762999, rs999556, rs4958881 and rs3792783, between VKH patients and healthy controls (Pc>0.05). No significant difference was noted in allele or genotype frequencies of the tested 7 SNPs between BD patients and healthy controls. Analysis of extraocular clinical findings, did not reveal an association of the TNIP1 gene polymorphisms with BD or VKH syndrome subgroups. A TNIP1 polymorphism may be a risk factor for VKH syndrome in Han Chinese.
    PLoS ONE 01/2014; 9(5):e95573. · 3.53 Impact Factor
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    ABSTRACT: Recent studies show that the aryl hydrocarbon receptor (AhR) is involved in immune responses. AhR is activated following interaction with its ligands, such as 6-formylindolo[3,2-b]carbazole (FICZ) and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). In this study, we investigated the role of AhR activation by its endogenous ligands in the pathogenesis of ocular Behcet's disease (BD). The expression of AhR was significantly decreased in active BD patients as compared to inactive BD patients and normal controls. Both FICZ and ITE inhibited Th1 and Th17 polarization and induced the expression of IL-22 by PBMCs and by CD4(+)T cells in active BD patients and normal controls. Stimulation of purified CD4(+)T cells with FICZ or ITE caused a decreased expression of RORC, IL-17, IL-23R, and CCR6 and an increased phosphorylation of STAT3 and STAT5. The present study suggests that a decreased AhR expression is associated with disease activity in BD patients. The activation of AhR by either FICZ or ITE was able to inhibit Th1 and Th17 cell polarization. Further studies are needed to investigate whether modulation of AhR might be used in the treatment of BD.
    Mediators of Inflammation 01/2014; 2014:195094. · 3.88 Impact Factor
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    ABSTRACT: Abstract Purpose: Vogt-Koyanagi-Harada (VKH) syndrome is a multisystem disorder presumed to be mediated by an autoimmune response. Recent studies have shown that interleukin (IL) 25 was involved in the T-cell immune response. This study analyzed the expression and potential role of IL-25 in the pathogenesis of VKH syndrome. Methods: The IL-25 serum levels were determined by enzyme-linked immunosorbent assay (ELISA). The IL-1β, IL-6, and TNF-α level in supernatants of PBMCs cultured with LPS in the absence or presence of recombinant(r) IL-25 was detected by ELISA. Results: A significantly decreased serum IL-25 level was found in VKH patients. In vitro experiments showed that rIL-25 was able to significantly inhibit the production of IL-1β, IL-6, and TNF-α by PBMCs from active VKH patients. Conclusions: IL-25 may be involved in the development of VKH syndrome, possibly by inhibiting the expression of proinflammatory cytokines.
    Ocular immunology and inflammation 12/2013; · 0.72 Impact Factor
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    ABSTRACT: Purpose: The aim of the study was to determine the association of macrophage migration inhibitory factor (MIF )gene polymorphisms with Vogt-Koyanagi-Harada (VKH) syndrome. Methods:A total of 600 Han Chinese VKH patients and 600 healthy controls were genotyped for rs755622 and rs2096525 of MIF by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Data were analyzed by χ2 analysis. Results:Genotype distribution in controls was in Hardy-Weinberg equilibrium. The frequencies of the rs755622 GG genotype and G allele were significantly lower in VKH patients compared with controls (pc = 0.006 and 0.016 ). Stratification analysis showed decreased frequencies of the rs755622 GG genotype and G allele in patients respectively with headache, tinnitus, alopecia, poliosis, or vitiligo compared with controls (all pc<0.05). Rs2096525 genotype and allele frequencies were not different between VKH patients and controls. However a lower frequency of the rs2096525 TT genotype was observed in patients with headache compared with controls (pc<0.05). The frequencies of the rs2096525 T allele in patients with headache or vitiligo were significantly decreased compared with controls (pc = 8.54×10-4 and 0.012). In addition, the results showed a significantly increased frequency of the combined rs755622/rs2096525 CT haplotype and a decreased frequency of the GT haplotype in VKH patients compared with controls. Conclusions: Our study identified a strong association of rs755622 with VKH syndrome and certain clinical features. rs2096525 was associated with certain clinical features of VKH syndrome. The results also suggested that the CT and GT haplotypes were associated with VKH syndrome.
    Investigative ophthalmology & visual science 11/2013; · 3.43 Impact Factor
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    ABSTRACT: To test whether singlenucleotidepolymorphisms(SNPs) of the four Vitamin D family genes(DHCR7, CYP2R1, CYP27B1 and CYP24A1) previously associated with several autoimmune diseases, are associated with ocular Behçet disease, Vogt-Koyanagi-Harada (VKH) syndrome, acute anterior uveitis with ankylosing spondylitis (AAU+ankylosing spondylitis+) or pediatric uveitis in the Chinese Han population. Prospective case control study METHODS: Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)and the genotypes were verified with direct sequencing. The first stage study comprised 400 ocular Behçet disease patients, 400 VKH syndrome patients, 218 AAU(+)ankylosing spondylitis(+) patients, 400 pediatric uveitis patients and 600 healthy subjects from Chinese Han populations. The second stage included 427 ocular Behçet disease patients and 1000 healthy Chinese Han subjects. Allele and genotype frequencies were compared between patients and controls using the χ2 test. In the first stage study, only the frequencies of the rs12785878/DHCR7 genotype TT and T allele were significantly higher in ocular Behçet disease patients (p Bonferroni correction (pc) = 0.036; pc = 0.008, respectively) compared with controls among six SNPs. No associations could be detected for VKH, AAU(+)ankylosing spondylitis(+) or pediatric uveitis. A second stage and combined study confirmed the association of rs12785878/DHCR7 TT genotype and T allele with ocular Behçet disease(pc = 3.28E-04, OR = 1.506, 95% CI 1.248 to 1.818; pc = 2.82E-05, OR = 1.339, 95% CI 1.188 to 1.508, respectively). This study provides evidence that the DHCR7 gene is involved in the susceptibility to ocular Behçet disease.
    American Journal of Ophthalmology 10/2013; 157(2):488-94. · 4.02 Impact Factor

Publication Stats

2k Citations
488.45 Total Impact Points

Institutions

  • 2006–2014
    • Maastricht Universitair Medisch Centrum
      Maestricht, Limburg, Netherlands
  • 2004–2014
    • Maastricht University
      • Oogheelkunde
      Maestricht, Limburg, Netherlands
  • 2013
    • Xinjiang Medical University
      Ouroumtchi, Xinjiang Uygur Zizhiqu, China
  • 2004–2013
    • Wageningen University
      • Division of Division of Dierlijkeproductie systemen
      Wageningen, Gelderland, Netherlands
  • 2008–2012
    • Chongqing Medical University
      Ch’ung-ch’ing-shih, Chongqing Shi, China
    • Sun Yat-Sen University Cancer Center
      Shengcheng, Guangdong, China
  • 2005–2012
    • Sun Yat-Sen University
      • State Key Laboratory of Oncology
      Guangzhou, Guangdong Sheng, China
  • 2011
    • Case Western Reserve University
      • Division of Infectious Diseases and HIV Medicine
      Cleveland, OH, United States
    • Guangdong Academy of Medical Sciences and General Hospital
      Shengcheng, Guangdong, China
  • 2002–2003
    • Sun Yat-Sen University of Medical Sciences
      中山, Guangdong, China
    • Zhongshan University
      中山, Guangdong, China
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands