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Objective To explore whether tumor necrosis factor receptor-associated protein 1 (TRAP1)gene copy number variation was associated with susceptibility and clinical characteristics of systemic lupus erythematosus (SLE).Methods The study enrolled 304 SLE patients and 391 healthy controls.They were used to investigate the association between TRAP1 gene copy number variation and SLE susceptibility.Then,304 SLE patients were divided into copy number=2 group and copy number＞2 group to study the association between TRAP1 gene copy number variation and disease activity or clinical characteristics of SLE.AccuCopyTM Kit was used to detect the TRAP1 gene copy number.Data analyses were performed by SPSS 10.01 software.The suitable method was selected among t test,rank sum test and x2 test for analysis based on the data type and distribution,univariate and multivariate logistic regression analysis were performed to investigate the associ-ation between TRAP1 gene copy number variation and susceptibility and clinical characteristics of SLE.Results The copy number variation of TRAP1 gene showed an association with the susceptibility to SLE crude OR=5.257,95％CI (1.108,24.937),P=0.037;the adjusted OR=5.578,95％CI (1.172,26.556),P=0.031].There was no association between TRAP1 gene copy number variation and SLE disease activity index (SLEDAI) score (Z=-0.117,P=0.907).The copy number variation of TRAP1 gene had a marginal association with skin lesions in SLE [OR=0.130,95％CI (0.016,1.069),P=0.058],but it disappeared after adjusting for potential confounders [OR=0.288,95％CI (0.029,2.831),P=0.286,PBH=0.808].There was no correlation between TRAP1 gene copy number variation and arthritis,alopecia,oral ulcers,fever,hematologic disorder,lupus nephritis as well as photosensitivity in SLE [x2=0.751,OR=1.234,95％CI (0.767,1.988),P=0.386].No multiplicative interaction was found between TRAP1 gene copy number variation and age or body mass index (BMI) [age:x2=0.751,OR=1.234,95％CI (0.767,1.988),P=0.386;BMI:x2=0.282,OR=1.172,95％CI(0.652,2.109),P=0.596].Conclusions The copy number variation of TRAP1 gene may be associated with susceptibility to SLE.Increased TRAP1 gene copy number may be a risk factor for SLE.
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Objective To explore the prevalence and reference value of disease features of patients with spondyloarthritis. Methods Spondyioarthritis features and laboratory indexes and radiographic indexes of 505 patients with spondyloarthritis (SpA) including 353 patients with ankylosing spondylitis (AS), 62 patients with non-radiographic axial spondyloarthritis (nr-axSpA) and 90 patients with peripheral spondyloarthritis (pSpA) were recorded. One-way analysis of variance, Kruskal-Wallis test, x2-test, Logistic regression were used for statistical analysis. Results Sex ratio ( x2=20.673, P<0.01), age ( x2=22.258, P<0.01), disease duration ( x2=76.052, P<0.01) were different among AS, nr-axSpA and pSpA. Besides, Bath ankylosing spondylitis disease activity index (BASDAI), ankylosing spondylitis disease activity score (ASDAScrp), erythrocyte sedimentation rate (ESR), C-reactionprotein (CRP) and Bath ankylosing spondylitis functional index (BASFI)were different among SpA subgroups ( x2/F=13.196-40.028, P<0.01). Prevalence of inflammatory back pain, peripheral arthritis, preceding infection, positive human lymphocyte antigen (HLA)-B27 and elevated CRP were different among SpA subgroups ( x2=11.416, 32.657, P<0.01). Prevalence of dactylitis in SpA with positive HLA-B27 was lower than that in SpA with negative HLA-B27 ( x2=5.414, P=0.02). Prevalence of enthesitis and dactylitis in SpA patients with peripheral arthritis was higher than that in SpA without peripheral arthritis involvement ( x2=7.177, 14.428, P<0.01). Prevalence of good response to Non-steroid anti-inflammatory drugs. (NSAIDs) in patients with anterior uveitis involvement was higher than SpA without anterior uveitis involvement ( x2=4.578, P=0.032). SpA patients were stratified by total number of SpA features into 4 subgroups (n≤1, n=2, n=3, n≥4). Prevalence of inflammatory back pain, positive HLA-B27, good response to NSAIDs were the top three in all subgroups. Inflammatory back pain and HLA-B27 (+) were risk factors for axSpA (OR=3.254, 3.323, P<0.01). Peripheral arthritis, dactylitis, and preceding infection were risk factors for pSpA (OR=3.759, 4.134, 17.044, P<0.01). Conclusion Inflammatory back pain, HLA-B27 (+) and good response to NSAIDs should be emphasized for the diagnosis of SpA. Inflammatory back pain and HLA-B27(+) always means axSpA. Peripheral arthritis, dactylitis and preceding infection always indicates pSpA.
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Objective This study aimed to investigate whether the copy numbers of the CCL3L1 (Chemokine C-C-Motif Ligand 3 Like Protein 1) gene were associated with susceptibility to ankylosing spondylitis (AS). Methods A total of 806 Chinese individuals including 405 AS patients and 401 healthy controls were enrolled. The CCL3L1 gene copy number was measured by a custom-by-design Multiplex AccuCopyTM Kit based on a multiplex fluorescence competitive polymerase chain reaction (PCR) principle, and 50 samples were randomly selected using the fluorescent quantitative PCR method to verify copy number. Main statistical method was t test, chi-square test and logistic regression model. Results There were no statistically significant differences between the case group and control group in age and gender ( t=1.77, P=0.076, χ2=1.14, P=0.289). The copy number of CCL3L1 gene ranged from 0 to 13 in both AS patients and the controls. After copy numbers were classified into 3 categories by 3, we did not find significant difference between the two groups ( χ2=0.591, P=0.669). And regression analyses also did not support the hypothesis that CCL3L1 gene copy number variation (CNV) could be an impact factor to the severity or function indexes of AS patients ( χ2=0.341, P=0.804 and χ2=0.472, P=0.774, respectively). Conclusion We suggest that the copy number of the CCL3L1 gene does not have a role in the susceptibility and the severity or function to AS.
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Objective To investigate the value of tumor necrosis factor (TNF)-α receptor gene,TNFRSF1A+36A/G(rs767455) and-383A/C(rs2234649),TNFRSF1B+196T/G(rs1061622) single nucleotide polymorphism (SNP) for the susceptibility to ankylosing spondylitis (AS) and the relationship between SNP and AS.T test,Chi-square test,and ANOVA were used for statististical analysis.Methods Two hundred and fifteen patients who had definite diagnosis of AS and 216 healthy blood donors were involved in this study.SNPs of TNF-α receptor gene:TNFRSF1A +36A/G(rs767455),-383A/C(rs2234649) and TNFRSF1B+196T/G (rs1061622) were detected with the ligase detection reaction (LDR-PCR) method.Results ① Distribution frequencies of A alleles(86.8％,91.5％) and G alleles (13.2％,8.5％) of TNFRSF1A(rs767455) in AS and controls were significantly different with each other (x2=4.627,P=0.0315),while the distribution frequency in group of homozygotes (AA or GG genotype) in AS and controls were 74.6％(150/201) and 83.9％(177/211),the frequencies in group of heterozygotes (AG) were 25.4％ (51/201) and 16.1％(34/211)(x2=5.390,P=0.020).Frequency of alleles and the genotypes of TNFRSF1A (rs2234649) and TNFRSF1B (rs1061622) between AS and control group were similar(P＞0.05).It also demonstrated that TNF-αreceptor gene haplotype (rs1061622T-rs2234649A-rs767455G) carriers apparently increased the susceptibility to AS (11.5％ vs 6.9％)(OR:1.753,95％CI:1.078～2.852,P=0.022).② Analysis of variance found that the duration of morning stiffness (F=3.168,P=0.044) and peripheral joint tenderness counts (F=4.598,P=0.011) among the three genotype groups of TNFRSF1B (rs1061622) in patient with AS were evidently differed with each other.Bath AS functional index (BASFI) among different genotype groups of TNFRSF1A (rs2234649) in AS had remarkable diversity (F=5.783,P=0.004).None of above indicators among groups of different genotypes of TNFRSF1A (rs767455) in AS were uniform (P＞0.05).③ Forty-four patients were treated with TNF-α antagonist (entanercept),25 mg,subcutaneous injection,twice weekly for 3 months,then followed with Sulfaslazine (SASP) 2.0 g/d and Celecoxib 0.4 g/d for another 9 months.ASAS20 was the primary endpoint for the evaluation of therapeutic effect at the visit of 3 month and 12 month.No associations were found between SNP and short or long term outcome of treatment with TNF-α antagonist in AS (P＞0.05).Conclusion TNFRSF1A (rs767455) SNP correlates with susceptibility to AS in Anhui Han local patients.Carriers of TNF-α receptor gene haplotype (rs1061622T-rs2234649A-rs767455G) may increase the susceptibility to AS.SNP of TNFRSF1B (rs1061622) is associated with disease activity in AS,while SNP of TNFRSF1A(rs2234649)relates to functional index of the disease.There is no association between SNP of TNFRSF1A / TNFRSF1B and short or long term outcome of treatment with TNF-α antagonist in AS.
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Objective To investigate the relationship between single-nucleotide polymorphism (SNP)in receptor activator for nuclear factor-κB ligand (RANKL),osteoprotegerin (OPG) gene and rheumatoid arthritis (RA).Methods In our study,3 SNPs in the genes of OPG (2 SNP:rs2073618,rs3102735) and RANKL (1 SNP:rs2277438) by ligase detection reactions from 200 RA and 201 controls were examined.BMD values of different areas were assessed using dual-energy X-ray absorptiometry.Clinical and laboratory parameters were collected.Analysis of variance,t-test and x2 test were used for statistical analysis.Results No signi-ficant differences in the distribution of the alleles and genotypes were observed between case group and the control group (P＞0.05).The haplotype analysis for RANKL and OPG SNPs showed that the rs2073618/rs2277438/rs3102735 GGG haplotype could reduce the risk of RA (1.5％ vs 6.0％,P=0.008; OR 0.216;95％CI:0.081 to 0.575) and the GAG haplotype increased the risk of RA (14.5％ vs 8.4％,P=0.007; OR 1.862,95％CI:1.179 to 2.943).Patients with RANKL-rs2277438 AA or GG genotypes (n=6) had significantly higher BMD values compared to those with AG genotypes (n=39) at spine lumber 3 (1.05±0.22 vs 0.93±0.26,t=2.314,P=0.023),spine lumber 4 (1.06±0.24 vs 0.94±0.28,t=2.27,P=0.030),spine lumber 2-4 (1.04±0.21 vs 0.89±0.28,t=2.788,P=0.007).The tender joint counts (13±7 vs 10±6),tender joint index (19±11 vs 13±9),and VAS score (5.7±1.9 vs 4.8±1.8) differed significantly between patients with the OPG-rs2073618 CC or GG genotypes (n=60) and GC genotypes (n=40).Conclusion The rs2073618/rs2277438/rs3102735GGG haplotype may be protective against RA,while GAG haplotype may increase the susceptibility to RA.RANKL gene SNP rs2277438 may affect BMD value at spine lumber,and OPG gene SNP rs2073618 may influence the disease activity of RA patients.
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Objective To evaluate the association between recurrent miscarriages and insulin resistance.Methods The case-control studies on the association between recurrent spontaneous abortion and insulin resistance from June 1996 to April 2012 were collected from Medline,Elsevier,Chinese Journal Fulltext Database,Chinese Biological Medicine Database,data base of Wanfang,Springer link and EMBASE.RevMan 5.1 software was used for Meta analysis.Results According to the included criteria,7 clinical trials were finally selected.Total 467 cases with recurrent pregnancy loss were enrolled in study group,while 413 women with no history of abnormal pregnancies were enrolled in control group.No significant difference was found in average age and body mass index between the two groups (P ＞ 0.05).Meta analysis results showed that the level of fasting glucose was no statistical difference between study group and control group (WMD =2.27,95％ CI:-1.11 to 5.65,P ＞0.05); fasting insulin level was higher 2.05 mU/L in study group than that of in control group,the difference was statistically significant (WMD =2.05,95％ CI:1.03 to 3.08,P ＜ 0.01).Case number of study group on Homa-insulin resistance ＞ 4.5 was more than that of control group (OR =3.36,95％ CI:1.72 to 6.57,P ＜ 0.01).Case number of study group on glucose/insulin ratio ＜ 4.5 was more than that of the control group,statistical difference was found (OR =3.37,95％ CI:1.90 to 5.99,P ＜ 0.01).Conclusion Insulin resistance is associated with the susceptibility to recurrent miscarriages,and it may contribute to the occurrence of recurrent miscarriages.
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ObjectiveTo investigate the association between the FCRL5 gene (rs6427384 and rs12036228) single nucleotide polymorphism(SNP) and patients with ankylosing spondylitis (AS). Methods SNP of FCRL5 gene (rs6427384 and rs12036228) was analyzed in 169 patients with AS and 184 healthy controls by ligase detection reaction based on high temperature(LDR)-PCR. The distribution of FCRL5 genotypes and allele frequencies were detected between the two groups. Chi-square test, one-way ANOVA were used for statistical analysis. ResultsSignificant differences were found in the distribution of allele frequencies of FCRL5 gene between AS patients and health controls(P＜0.05). The C allele frequencies of FCRL5 gene at positions of rs6427384 and rs12036228 were 17.3％, 92.3％ and 25.0％, 87.2％ respectively in the AS group and the control group. And the T allele frequencies of rs6427384 and rs12036228 were 82.7％, 7.7％ and 75.0％, 12.8％ in the AS group and the control group. The percentages of CC, CT and TT genotype(rs6427384) were 3.7％, 27.2％, and 69.1％ in the AS group, which were significantly different from those of the control group(3.9％, 42.2％ and 53.9％ ) (x2=8.7637, P=0.0125 ). Staging of sacroiliitis in X ray were significantly different during AS patients whose genotype represented as CC, CT and TT (rs6427384)(x2=34.159, P=0.0001 ). Incidences of the initial symptoms (low back pain or inflammation of periphery joint)in the AS group were obviously differed among patients with different genotypes (rs6427384) (x2=7.254, P=0.027), so did the mean duration of morning stiffness (F=4.159, P=0.018) and the average scores of BASDAI (F=4.461, P=0.014). Incidences of the initial symptoms in the AS group were also conspicuously different between the AS patients with different genotypes (rs 12036228 ) (x2=6.640, P=0.036 ). ConclusionOur study suggests that the SNP(rs6427384 and rs12036228) of FCRL5 may be a susceptibility factor for AS in Anhui Han population and the genotype may influence the clinical phenotype of AS.
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Objective To investigate the association between interleukin(IL)-1F7 gene (rs3811047)single nucleotide polymorphism (SNP) and ankylosing spondylitis (AS). Methods SNP of IL-1F7 gene (rs3811047) was analyzed in 158 patients with AS and 181 healthy controls by ligase detection reaction based on high temperature ligase (LDR-PCR). The distribution of IL-1 F7 (rs3811047 ) genotypes and allele frequencies were detected between the two groups. Results Significant differences were found in the distribution of IL-1F7(rs3811047 ) genotypes and allele frequencies between AS patients and healthy controls. The frequency of A allele of IL-1F7 gene at positions rs3811047 was 12.03% and 17.68% in AS group and the control group,and the frequency of G allele was 87.97%, 82.32%, respectively (x2=4.2204, P=0.0399). The percentage of AA, AG and GG genotype was 0, 24.05%, 75.95% in AS group, which differed from the controls group (2.76%, 29.83%, 67.41% ). The difference had remarkable statistical significance (x2=6.2675, P=0.043).The positive rate of HLA-B27 in AS patients which represented as AG genotype was 70.27% (26/37),remarkably lower than that in AS patients which represented as GG genotype 94.23% (98/104), the difference was statistically significant (x2=2.168, P=0.030), erythrocyte sedimentation rate and C reactive protein levels were conspicuously lower than that in GG genotype (t=2.971, P=0.013; t=3.300, P=0.001 ). Conclusion Our study suggests that the SNP (rs3811047) of IL-1F7 may be a susceptibile factor for AS in Anhui Han population, the genotype may influence the clinical phenotypes of AS.Patients who carry the A allele may have less inflammation than patients who do not carry the A allele.