Prevalence and clinical features of systemic diseases in Chinese patients with uveitis.

PURPOSE: Systemic diseases are frequently associated with uveitis but are often not recognised by clinicians. An estimate of the prevalence in a large-scale uveitis population is essential for understanding the epidemiological profile and may be helpful for clinical practice. DESIGN: A nationwide survey. METHODS: Data were obtained from a national database which included the registration of uveitis cases from 23 provinces, 5 autonomous regions and 4 municipalities across mainland China. The primary outcome was identification of a systemic disease associated with uveitis. RESULTS: From April 2008 through August 2018, 15 373 uveitis patients were included in the study. Males accounted for 52.9%, and the mean (SD) age of uveitis onset was 35.4 (15.9) years. After standardisation for age, the prevalence of systemic disease among patients with uveitis was 30.8% (95% CI, 30.1% to 31.6%). Vogt-Koyanagi-Harada disease (VKH; age-standardised prevalence, 12.7%; 95% CI, 12.1% to 13.2%), Behçet's disease (BD; 8.7%; 95% CI, 8.3% to 9.2%), ankylosing spondylitis (AS; 5.0%; 95% CI, 4.6% to 5.3%) and juvenile idiopathic arthritis (JIA; 1.2%; 95% CI, 1.0% to 1.3%) were the most common entities among 36 different forms of systemic diseases identified. The prevalence was significantly higher in males (37.0%; 95% CI, 36.0% to 38.1%) than in females (23.6%; 95% CI, 22.6% to 24.6%), and also higher in bilateral uveitis patients (41.2%; 95% CI, 40.2% to 42.2%) compared with unilateral cases (14.3%; 95% CI, 13.4% to 15.2%), and was highest in panuveitis (59.5%; 95% CI, 58.2% to 60.8%). CONCLUSION: Approximately one third of uveitis patients in this nationwide survey have an associated systemic disease, whereby VKH, BD, AS and JIA are the most frequent entities seen in China.

Association of IFN-γ polymorphisms with ankylosing spondylitis risk.

The case-control study was designed to investigate the genetic effects of interferon-gamma (IFN-γ) rs2069727 and rs1861494 polymorphisms on ankylosing spondylitis (AS) susceptibility in a Chinese Han population. Blood samples were collected from 108 AS patients and 110 healthy controls. IFN-γ polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Hardy-Weinberg equilibrium (HWE) test was performed in control group. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using chi-square test to evaluate the association between AS susceptibility and IFN-γ polymorphisms, and the results were adjusted by logistic regressive analysis. The frequency of rs2069727 CC genotype was much higher in cases than that in controls, suggested its significant association with increased AS risk (adjusted OR = 5.899, 95% CI = 1.563-22.261; P = .009). In addition, C allele also showed close association with increased risk of AS (adjusted OR = 2.052, 95% CI = 1.286-1.704, P  = 0 .003). While the genotype and allele frequencies of IFN-γ rs1861494 polymorphism were not significantly different between patients and controls (P  > 0.05 for all), IFN-γ rs2069727 polymorphism is significantly associated with increased AS risk in a Chinese Han Population.

MHC associations of ankylosing spondylitis in East Asians are complex and involve non-HLA-B27 HLA contributions.

BACKGROUND: The association of HLA-B*27 with AS is amongst the strongest of any known association of a common variant with any human disease. Nonetheless, there is strong evidence indicating that other HLA-B alleles are involved in the disease. European ethnicity studies have demonstrated risk associations with HLA-B*40 and multiple other HLA-B, HLA-A, and HLA class II alleles, and demonstrated that in that ethnic group, the amino acid sequence at position 97 in HLA-B is the key determinant of HLA associations with AS. A recent study in Korean AS cases and controls additionally identified association at HLA-C*15:02. In the current study, we examined the MHC associations of AS in an expanded East Asian cohort. METHODS: A total of 1637 Chinese, Taiwanese, and Korean AS cases meeting the modified New York Criteria for AS, and 1589 ethnically matched controls, were genotyped with the Illumina Immunochip, including a dense coverage of the MHC region. HLA genotypes and amino acid composition were imputed using the SNP2HLA programme using the Han-MHC reference panel based on the data of Han Chinese subjects (n = 9689), and association tested using logistic regression controlling for population stratification effects. RESULTS: A strong association was seen with HLA-B*27 (odds ratio (OR) = 205.3, P = 5.76 × 10-244). Controlling for this association, the strongest risk association is seen with HLA-C*15 at genome-wide significant level (OR = 7.62, P = 9.30 × 10-19), and confirmed association is also seen with HLA-B*40 at suggestive level (OR = 1.65, P = 2.54 × 10-4). At amino acid level, the strongest association seen in uncontrolled analysis was with histidine at position 114 in HLA-B (P = 7.24 × 10-241), but conditional analyses suggest that the primary amino acid associations are with lysine at position 70 and asparagine at position 97. Restriction of the ERAP1 association with HLA-B27-positive AS, previously reported in European subjects, was confirmed in East Asians. CONCLUSIONS: This study confirms in East Asians that the HLA associations of AS are multiple, including previously reported associations at HLA-B*27, HLA-B*40, and HLA-C*15, as well as novel association with HLA-DQB1*04. The HLA-B associations are driven by the amino acids at positions 70 and 97, in the B pocket of HLA-B.

Association of rs27044 and rs30187 polymorphisms in endoplasmic reticulum aminopeptidase 1 gene and ankylosing spondylitis susceptibility: A meta-analysis.

BACKGROUND: The findings regarding association of endoplasmic reticulum aminopeptidase 1 (ERAP1) gene polymorphisms and ankylosing spondylitis (AS) susceptibility are inconsistent. Our aim is to appraise and merge the existing evidence on the relationship of rs27044 and rs30187 polymorphisms in ERAP1 gene and susceptibility to AS. METHODS: Electronic databases of PubMed, Web of Science, EMBASE, Cochrane Library, Wanfang, and CNKI were retrieved for relevant publications. The search was conducted from inception to 10 June, 2019. Studies on the association of rs27044 and rs30187 polymorphisms and risk of AS were included. Quality evaluation was carried out using Newcastle-Ottawa Scale (NOS). Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to appraise the associations under allelic and genotypic models. RESULTS: In total, 26 case-control studies with 31 cohorts containing 17 223 AS patients and 36 915 controls were eligible for this meta-analysis. According to NOS, each study received ≥ 5 scores. The pooled data indicated that rs27044 and rs30187 polymorphisms were significantly associated with AS susceptibility in the overall population: rs27044, G versus C, OR = 1.24, 95% CI 1.16-1.33, P<.001; rs30187, T versus C, OR = 1.24, 95% CI 1.17-1.33, P<.001. When stratified by ethnicity, rs27044 appeared to be significantly correlated with AS in both Asians and Caucasians. For rs30187, despite positive association being observed under the allelic model in both Asians and Caucasians, the findings of genotypic comparisons supported the association only existed in Caucasians but not Asians. CONCLUSION: This study suggests that rs27044 and rs30187 polymorphisms are significantly associated with increased risk of AS, especially in Caucasians.

Gene-gene interaction and association of Wnt/Β-catenin signalling pathway gene polymorphisms with ankylosing spondylitis susceptibility in the Chinese Han population.

Objectives: To explore the genetic interaction between Wnt/ß-catenin signalling pathway genes and ankylosing spondylitis (AS) in the Chinese population.Methods: Six single-nucleotide polymorphisms (SNPs) in DKK1, LRP5, LRP6, and SOST genes were genotyped in 673 AS patients and 687 healthy controls by using SNPs can Technic. Single marker genetic association analysis was performed. Haplotypes were constructed after linkage disequilibrium analysis; additive, multiplicative, and higher-order interactions were analysed.Results: The DKK1 gene rs1569198 polymorphism was significantly associated with AS susceptibility in females (χ2 = 4.55, p = .03), but the association disappeared after Bonferroni correction. Moreover, a haplotype (T-G) in the DKK1 gene showed a protective role in AS susceptibility in females (p = .04). Significant additive interactions were observed between DKK1: rs1896368 and LRP5: rs3736228, relative excess risk due to interaction (RERI) = 0.40, 95% CI = 0.08 - 0.71; attributable proportion due to interaction (AP) = 51%, 95% CI = 0.07 - 0.94, DKK1: rs1569198 and LRP5: rs3736228 (RERI = 0.49, 95% CI = 0.12 - 0.86; AP = 49%, 95% CI = 0.17 - 0.82), LRP5: rs3736228 and SOST: rs4792909 (RERI = 0.33, 95% CI = 0.002 - 0.65; AP = 41%, 95% CI = 0.01 - 0.81) in the dominant model.Conclusions: Our research implies a potential gene-gene interaction, thus revealing the importance of the Wnt/ß-catenin signalling pathway for understanding the genetic architecture of AS.

Comparison of ankylosing spondylitis and non-radiographic axial spondyloarthritis in a multi-ethnic Asian population of Singapore.

OBJECTIVES: To compare clinical characteristics, disease activity, patient-reported outcomes and associated comorbidities between patients with ankylosing spondylitis (AS) and non-radiographic axial spondyloarthitis (nr-axSpA) in a multi-ethnic Asian population of Singapore. METHODS: We used data from the PREcision medicine in SPONdyloarthritis for Better Outcomes and Disease Remission (PRESPOND) registry in Singapore General Hospital. All patients fulfilled 2009 Assessment in AS International Working Group classification criteria for axial SpA (axSpA). Of these, all AS patients fulfilled the 1984 modified New York criteria. Baseline characteristics, medications, disease activity, patient-reported outcomes and inflammatory markers were recorded using standardized questionnaires. RESULTS: Two hundred and sixty-two axSpA patients (82% Chinese, 79% male) were included. Mean age (SD) at diagnosis was 32.4 (13.1) years, which was similar between AS and nr-axSpA patients. AS patients were older (mean age 42.7 [13.5] vs 37.4 [13.8] years, P = 0.02), had longer disease duration (mean disease duration 10.9 [8.7] vs 6.4 [4.8] years, P < 0.01), higher Bath Ankylosing Spondylitis Metrology Index (BASMI) (mean BASMI 3.1 [2.3] vs 1.5 [1.5], P < 0.01), more frequently human leukocyte antigen (HLA)-B27 positive (82% vs 68%, P = 0.03), associated with uveitis (33% vs 17%, P = 0.03), and hypertensive (17% vs 0%, P < 0.01) compared to nr-axSpA, respectively. Nr-axSpA patients had higher Bath Ankylosing Spondylitis Global Score (BAS-G) (mean BAS-G 46.9 [16.8] vs 38.6 [20.6], P < 0.01), Bath Ankylosing Spondylitis Disease Activity Index (mean [SD] 4.2 [1.6] vs 3.5 [1.9], P = 0.02) and AS quality of life (ASQoL) (mean ASQoL 4.9 [4.8] vs 3.5 [4.1], P = 0.04) scores compared to AS patients respectively at baseline. Patient global assessment, Bath Ankylosing Spondylitis Functional Index, AS Disease Activity Score - C-reactive protein (CRP), Health Assessment Questionnaire, Short-Form 36 physical component summary and mental component summary were similar in both groups at baseline, as were medications used and mean erythrocyte sedimentation rate and CRP. CONCLUSIONS: In our multi-ethnic Asian cohort, patients with AS are more likely to be HLA-B27 positive, have uveitis, hypertensive, and have poorer spinal mobility, while nr-axSpA patients tend to experience poorer well-being and quality of life.

Distribution of HLA-B*27 Subtypes in Patients with Ankylosing Spondylitis in Local Population.

OBJECTIVE: To compare the distribution of HLA-B*27 subtypes in healthy controls and in ankylosing spondylitis (AS) patients of different ethnic groups from Pakistan. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from April 2016 to October 2017. METHODOLOGY: Forty-nine HLA-B*27 positive, unrelated AS patients and 18 HLA-B*27 positive healthy BMT/renal transplant donors were selected for this study. Typing of the HLA-B27 alleles was performed by the polymerase chain reaction-sequence-specific primer (PCR-SSP). RESULTS: There was a wide number of HLA-B*27 subtypes and an elevated frequency of the B*2707 allele in the AS patients. The allele B*2706 seems to have a protective role in the population studied because it was found only in the healthy controls. HLA-B*27:03 and 07 were found predominant subtypes in Punjabis and Pathans, respectively. CONCLUSION: There were no significant differences for the distribution of B*27 subtypes between patients and controls (p >0.05).

HLA class I and II alleles in susceptibility to ankylosing spondylitis.

OBJECTIVE: To examine associations of HLA class I and class II alleles with ankylosing spondylitis (AS) in three cohorts of patients of European, Asian and African ancestry. METHODS: HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 and HLA-DPB1 alleles were genotyped in 1948 unrelated white and 67 African-American patients with AS from the Prospective Study of Outcomes in Ankylosing Spondylitis cohort, the North American Spondylitis Consortium and Australo-Anglo-American Spondyloarthritis Consortium, 990 white and 245 African-American Controls and HLA-B alleles in 442 Han Chinese patients with AS and 346 controls from Shanghai and Gansu, China. In addition to the case:control analyses, HLA-B*27-negative patients with AS were analysed separately, and logistic regression and 'relative predispositional effects' (RPE) analyses were carried out to control for the major effect of HLA-B*27 on disease susceptibility. RESULTS: Although numerous associations were seen between HLA alleles and AS in whites, among HLA-B*27-negative patients with AS , positive associations were seen with HLA-A*29, B*38, B*49, B*52, DRB1*11 and DPB1*03:01 and negative associations with HLA-B*07, HLA-B*57, HLA-DRB1*15:01, HLA-DQB1*02:01 and HLA-DQB1*06:02. Additional associations with HLA-B*14 and B*40 (B60) were observed via RPE analysis, which excludes the HLA-B*27 alleles. The increased frequency of HLA-B*40:01 and decreased frequency of HLA-B*07 was also seen in Han Chinese and African-Americans with AS. HLA-B*08 was decreased in whites with acute anterior uveitis. CONCLUSIONS: These data, analysing the largest number of patients with AS examined to date in three ethnic groups, confirm that other HLA class I and II alleles other than HLA-B*27 to be operative in AS predisposition.

Case-Control Study and Meta-Analysis Show a Weak Association between ANTXR2 Polymorphisms and Ankylosing Spondylitis in Chinese Han.

Previous studies have demonstrated associations of ANTXR2 gene polymorphisms with ankylosing spondylitis (AS). These associations differ depending on the ethnic populations and AS subgroups studied. Purposes of the current study were to evaluate the associations of 4 single nucleotide polymorphisms (SNPs) of the ANTXR2 gene with susceptibility to AS alone or AS in combination with acute anterior uveitis (AAU) in Chinese Han. Therefore, a case-control association study was performed in 880 AS+AAU-, 860 AS+AAU+, and 1700 healthy controls. Genotyping was performed using the iPLEXGold genotyping assay. Our results showed a weak association of rs6534639 AA genotype with AS+AAU+ patients (p=0.042), which was lost after correction for multiple comparisons. No other association was found between SNPs of ANTXR2 and susceptibility of AS+AAU- or AS+AAU+. A meta-analysis was performed to evaluate the associations of polymorphisms in the ANTXR2 gene with AS. Results showed a weak association of rs4389526 with AS susceptibility in all studies but failed to show an association of rs6534639 with AS in Chinese Han. Taken together, this study shows no association between ANTXR2 polymorphisms and AS susceptibility in a Chinese Han population, but meta-analysis showed that rs4389526 in the ANTXR2 gene was weakly associated with AS susceptibility in both Caucasian and Chinese Han patients.

Role of TNFRSF1A and TNFRSF1B polymorphisms in susceptibility, severity, and therapeutic efficacy of etanercept in human leukocyte antigen-B27-positive Chinese Han patients with ankylosing spondylitis.

The successful therapeutic use of anti-TNF biological agents in patients with ankylosing spondylitis (AS) indicates that tumor necrosis factor-α (TNF-α) and tumor necrosis factor receptor (TNFR) genes are involved in the pathogenesis of AS. TNF-α exerts its biological activity by binding to its cell surface receptors (p55 TNF-α receptor [TNFRI, encoded by the Tumor Necrosis Factor Receptor Superfamily Member 1A (TNFRSF1A)] and p75 receptor [TNFRII, encoded by the Tumor Necrosis Factor Receptor Superfamily Member 1B (TNFRSF1B)]. TNFRSF1A and TNFRSF1B may be related to AS, but the relevant studies are still limited. Therefore, we aim to explore the association between TNFRSF1A and TNFRSF1B polymorphisms and susceptibility and short- and long-term response to anti-TNF treatment in human leukocyte antigen-B27 (HLA-B27)-positive Chinese Han patients with AS.A total of 215 HLA-B27-positive patients with AS and 216 HLA-B27-positive matched controls were enrolled and genotyped for rs767455, rs2234649, and rs1061622. A subset of 50 AS patients was also studied for the association of these polymorphisms with the short- and long-term response to etanercept assessed by Assessment in Ankylosing Spondylitis 20 (ASAS20) and Assessment in Ankylosing Spondylitis 40 (ASAS40).Our data showed that rs767455 was associated with the susceptibility of AS, G allele of rs767455 exhibited an association with the risk of developing AS (OR = 1.63 (1.04-2.55), P = .032). Rs1061622 polymorphism was associated with total back pain and chest expansion. Only rs1061622 was significantly associated with long-term efficacy of etanercept: the TG genotype of rs1061622 worsened ASAS20 and ASAS40 responses at 12 months (P = .021 and .041, respectively).The results suggest that TNFRSF1A and TNFRSF1B polymorphisms were associated with susceptibility, severity, and the long-term therapeutic efficacy of etanercept of patients with AS.

Do ethnicity, degree of family relationship, and the spondyloarthritis subtype in affected relatives influence the association between a positive family history for spondyloarthritis and HLA-B27 carriership? Results from the worldwide ASAS cohort.

BACKGROUND: The Assessment of SpondyloArthritis international Society (ASAS) defines a positive family history (PFH) of spondyloarthritis (SpA) as the presence of ankylosing spondylitis (AS), acute anterior uveitis (AAU), reactive arthritis (ReA), inflammatory bowel disease (IBD), and/or psoriasis in first-degree relatives (FDR) or second-degree relatives (SDR). In two European cohorts, a PFH of AS and AAU, but not other subtypes, was associated with human leukocyte antigen B27 (HLA-B27) carriership in patients suspected of axial SpA (axSpA). Because the importance of ethnicity or degree of family relationship is unknown, we investigated the influence of ethnicity, FDR, or SDR on the association between a PFH and HLA-B27 carriership in patients suspected of axSpA. METHODS: Baseline data from the ASAS cohort of patients suspected of axSpA were analyzed. Univariable analyses were performed. Each disease (AS, AAU, psoriasis, IBD, ReA) in a PFH according to the ASAS definition was a determinant in separate models with HLA-B27 carriership as outcome. Analyses were stratified for self-reported ethnicity, FDR, and SDR. Analyses were repeated in multivariable models to investigate independent associations. RESULTS: A total of 594 patients were analyzed (mean [SD] age 33.7 [11.7] years; 46% male; 52% HLA-B27+; 59% white, 36% Asian, 5% other). A PFH was associated with HLA-B27 carriership in patients with a white (OR, 2.3, 95% CI, 1.4-3.9) or Asian ethnicity (OR, 3.1, 95% CI, 1.6-5.8) and with a PFH in FDR (OR, 2.9, 95% CI, 1.8-4.5), but not with a PFH in SDR (OR, 1.7, 95% CI, 0.7-3.8) or in other ethnicities. A PFH of AS was positively associated with HLA-B27 carriership in all subgroups (white OR, 7.1; 95% CI, 2.9-17.1; Asian OR, 5.7; 95% CI, 2.5-13.2; FDR OR, 7.8; 95% CI, 3.8-16.0; SDR OR, 3.7; 95% CI, 1.2-11.6). A PFH of AAU, ReA, IBD, or psoriasis was never positively associated with HLA-B27 carriership. In the multivariate analysis, similar results were found. CONCLUSIONS: In the ASAS cohort, a PFH of AS, but not of AAU, ReA, IBD, or psoriasis, was associated with HLA-B27 carriership regardless of white or Asian ethnicity or degree of family relationship. This cohort and two European cohorts show that a PFH of AS and possibly a PFH of AAU can be used to identify patients who are more likely to be HLA-B27-positive and therefore may have an increased risk of axSpA.

Simplified Chinese version of hip and knee replacement expectations surveys in patients with osteoarthritis and ankylosing spondylitis: cross-cultural adaptation, validation and reliability.

BACKGROUND: The Hospital for Special Surgery Hip Replacement Expectations Survey (HSS-THRES) and Knee Replacement Expectations Survey (HSS-TKRES) are widely used tools developed to assess patients' preoperative expectations for total hip and knee arthroplasty. This study aimed to translate and adapt the HSS-THRES and HSS-TKRES into Chinese versions (SC-THRES/TKRES) and evaluate their psychometric properties in patients with osteoarthritis (OA) and ankylosing spondylitis (AS). METHODS: Patients scheduled for total hip (104 hip OA and 51 AS) or knee replacements (101 knee OA) were recruited in this study. Confirmatory Factor Analysis (CFA) was used to evaluate structural validity. The internal consistency was assessed by the Cronbach's α coefficient. The intraclass correlation coefficient (ICC) was used to assess test-retest reliability. The construct validity was analyzed by evaluating the correlations between SC-THRES/TKRES and the Expectation WOMAC. The correlations with the Expectation WOMAC were tested against our hypotheses. We additionally compared preoperative expectations of AS patients to those of hip OA patients. RESULTS: The results of CFA for the SC-THRES and SC-TKRES demonstrated good fit. The results for the SC-THRES/TKRES revealed good test-retest reliability and good internal consistency (AS: ICC = 0.893, Cronbach's α = 0.815; hip OA: ICC = 0.878, Cronbach's α = 0.814; knee OA: ICC = 0.806, Cronbach's α = 0.808). The correlations between the SC-THRES/TKRES and the Expectation WOMAC were moderate (0.541 for AS, 0.490 for hip OA and 0.465 for knee OA), which were consistent with the hypotheses. CONCLUSION: The SC-THRES/TKRES are reliable, valid for the evaluation of Chinese patients with OA and AS undergoing total hip and knee arthroplasty. The surveys can be used as part of preoperative assessments. Meanwhile, additional research is needed to replicate these findings and to assess the content validity in a larger sample.

Polymorphisms in the Osteopontin Are Associated with Susceptibility to Ankylosing Spondylitis in a Han Chinese Population.

The aim of this study was to investigate whether osteopontin (OPN) variants are associated with susceptibility to ankylosing spondylitis (AS) in a Chinese population. Polymorphisms at the 9175th position in exon 7 of OPN and rs17524488 were genotyped using direct sequencing in 186 unrelated AS patients and 188 ethnically matched healthy controls. Serum concentration of OPN was measured by enzyme-linked immunosorbent assay (ELISA) in all participants. AS patients displayed significantly higher OPN serum levels than the controls (P < 001). A heterozygous, novel 9175 T>A in exon 7 of the OPN gene was found in this study. In healthy controls, subjects carrying the rs17524488 G/G genotype of the OPN display significantly higher OPN serum levels than the GG/GG genotype (P < 0.05). Plasma OPN level is implicated as an early diagnostic marker of AS. The novel 9175th- (exon 7) position polymorphism of OPN and rs17524488 were related to susceptibility to AS in a Chinese population, the rs17524488 G/G genotype may be involved in the pathogenesis of AS, and the precise molecular mechanism underlying the influence of OPN polymorphisms on the development of AS remains to be determined in the further prospective studies.

Association of TLR7 gene copy number variations with ankylosing spondylitis in a Chinese population: a case control study.

OBJECTIVES: To explore the association of TLR7 gene copy number variations (CNVs) with the susceptibility of ankylosing spondylitis (AS). METHODS: The case control study was performed in 649 Chinese Han patients with AS and 628 healthy controls. The copy numbers of TLR7 gene (2 fragments) were measured by AccuCopyTM methods. Chi-square and logistic regression models were performed to investigate the association of TLR7 gene CNVs with AS. Odds ratio (ORs) and 95% confidence intervals (CIs) was calculated to estimate AS risk and the Bonferroni correction was applied owing to multiple testing. RESULTS: The logistic regression analysis showed that one copy was significantly associated with AS susceptibility after Bonferroni correction (for the TLR7_1 fragment: OR=1.458, 95%CI(1.098,1.936), p=0.009; for the TLR7_2 fragment: OR=1.451, 95%CI (1.093,1.927), p=0.010), and this association still exists after adjustment of age and sex (for the TLR7_1 fragment: adjusted OR=2.066, 95%CI (1.318,3.238), p=0.002; for the TLR7_2 fragment: adjusted OR=2.061, 95%CI (1.315,3.230), p=0.002). However, logistic regression analysis stratified by gender showed a higher OR in males (for the TLR7_1 fragment: OR(95%CI)=7.987(3.756,16.983); for the TLR7_2 fragment: OR(95%CI)=7.947(3.738,16.897)) than in females (for the TLR7_1 fragment: OR(95%CI)=0.204(0.080,0.524); for the TLR7_2 fragment: OR(95%CI)=0.204(0.080,0.524)). CONCLUSIONS: We conclude that the lower copy number (=1) of TLR7 gene confers a risk factor for AS susceptibility in males but protective factor in females.

Single nucleotide polymorphisms of autophagy-related 16-like 1 gene are associated with ankylosing spondylitis in females: a case-control study.

AIMS: To investigate the associations of autophagy-related 16-like 1 (ATG16L1) gene single nucleotide polymorphisms (SNPs) with ankylosing spondylitis (AS) in a Chinese Han population. METHODS: Six hundred and forty-nine AS patients from the First Affiliation Hospital of Anhui Medical University and 628 matched controls were selected. Genotyping for five SNPs in the ATG16L1 gene (rs4663421, rs2241880, rs4663396, rs6758317 and rs6431655) was performed using the improved multiplex ligase detection reaction (iMLDR) method. Haplotypes were built after linkage disequilibrium (LD) analysis. All analyses were stratified by gender. RESULTS: Significant differences in the genotype frequencies at rs4663421 were found between female AS patients and female controls (P = 0.033). The frequencies of allele G of rs4663421 and allele C of rs6758317 were lower in AS patients than controls (odds ratio [OR] = 0.391, 95% CI = 0.175-0.876, P = 0.019; OR = 0.499, 95% CI = 0.263-0.949, P = 0.032, respectively) in females. However, no association remained significant after Bonferroni correction. rs4663396 and rs6758317 have been tested in high LD, and were used to construct three haplotypes: ht1 (CC), ht2 (TT) and ht3 (CT). The frequency of ht2 (TT) haplotype was higher in AS patients than controls (OR = 2.003, 95% CI = 1.053-3.808, P = 0.032) in females; similarly, no association existed after Bonferroni correction. CONCLUSIONS: Two SNPs (rs4663421 and rs6758317) and the TT haplotype of the ATG16L1 gene are possibly associated with AS susceptibility in a Chinese Han female population.

Lipid management among individuals with inflammatory arthritis in the national REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.

Objective Hyperlipidemia guidelines do not currently identify inflammatory arthritis (IA) as a cardiovascular disease (CVD) risk factor. We compared hyperlipidemia treatment of individuals with and without IA (rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis) in a large national cohort. Methods Participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were classified as having IA (without diabetes or hypertension); diabetes (but no IA); hypertension (but no diabetes or IA); or no IA, diabetes, or hypertension. Multivariable logistic regression models examined the odds of medical treatment among those with hyperlipidemia. Results Thirty-nine participants had IA, 5423 had diabetes, 7534 had hypertension, and 5288 had no diabetes, hypertension, or IA. The fully adjusted odds of treatment were similar between participants with IA and those without IA, hypertension, or diabetes. Participants with diabetes and no IA and participants with hypertension and no IA were twice as likely to be treated for hyperlipidemia as those without IA, diabetes, or hypertension. Conclusion Despite their higher CVD risk, patients with IA were as likely to be treated for hyperlipidemia as those without diabetes, hypertension, or IA. Lipid guidelines should identify IA as a CVD risk factor to improve CVD risk optimization in IA.

Association of polymorphisms in TNF and GRN genes with ankylosing spondylitis in a Chinese Han population.

The aim of this study is to investigate the association of the polymorphisms in tumor necrosis factor (TNF) and granulin (GRN) with ankylosing spondylitis (AS) in a Chinese Han population. Five single nucleotide polymorphisms (SNPs) covering TNF and six SNPs covering GRN were investigated in 861 Chinese Han AS patients and 864 healthy controls. For rs1799964, the C allele was linked to reduced risk of AS (p < 0.0001, OR = 0.60, 95% CI = 0.50-0.71). The carriers of the C/C homozygote showed a significantly lower risk of AS compared with the TT homozygote and the C/T heterozygote under the recessive model (p < 0.0001, OR = 0.23, 95% CI = 0.12-0.45). For rs1800629, the A allele was also linked to reduced risk of AS (p < 0.0001, OR = 0.54, 95% CI = 0.39-0.74). For rs1800630, the A allele was also linked to reduced risk of AS (p < 0.0001, OR = 0.59, 95% CI = 0.48-0.72). The carriers of the A/A homozygote showed a significantly lower risk of AS compared with the C/C homozygote and the A/C heterozygote under the recessive model (p < 0.0001, OR = 0.18, 95% CI = 0.07-0.47). For rs769178, the T allele was linked to increased risk of AS (p < 0.0001, OR = 2.59, 95% CI = 2.18-3.09). The carriers of the T/T homozygote showed a significantly higher risk of AS compared with the GG homozygote and the G/T heterozygote under the recessive model (p < 0.0001, OR = 3.34, 95 %CI = 1.95-5.72). There was no significant difference between the AS patients and the controls in the genotype or allele frequencies of rs361525. For GRN, there was no significant difference between the AS patients and the controls in the genotype or allele frequencies of rs25646, rs3760365, rs3785817, rs4792939, rs5848, rs850713 (p > 0.05). This study indicates that polymorphisms in TNF are related to AS, but polymorphisms in GRN are not related to AS susceptibility in a Chinese Han population.

Association of polymorphisms in ERAP1 and risk of ankylosing spondylitis in a Chinese population.

To explore the association between five polymorphisms in endoplasmic reticulum associated aminopeptidase 1 (ERAP1) gene and risk of ankylosing spondylitis (AS) in a Chinese population. A case-control study enrolled 250 AS patients and 250 healthy controls was carried out. The genotypes of involved polymorphisms (rs27037, rs27038, rs469876, rs27044 and rs27980) in ERAP1 were detected by Sequenom Mass-Array platform. There were significant differences of the level of WBC (white blood cell), Platelets, CRP (C-reactive protein) and ESR (erythrocyte sedimentation rate) between AS patients and controls (Pall<0.05). There was statistically association between ERAP1 rs27044 polymorphism and risk of AS, and the carriers with rs27044 CG genotype have an increased the risk for AS (CG versus GG, OR=1.70, 95% CI=1.10-2.62, P=0.015). However, we found no evidence for the association of rs27037, rs469876, and rs27980 polymorphisms in ERAP1 with AS risk. Our findings indicated that ERAP1 rs27044 polymorphism was associated with the susceptibility of AS.

El polimorfismo TNF-alfa-308 determina las manifestaciones clínicas y la respuesta al tratamiento de la espondilitis anquilosante en la etnia china Han / TNF-alpha-308 polymorphism determines clinical manifestations and therapeutic response of ankylosing spondylitis in Han Chinese

Antecedentes y objetivo: Existe un debate creciente acerca de si el factor de necrosis tumoral alfa (TNF-α)-308 está asociado a la espondilitis anquilosante (EA). El objetivo del presente estudio fue determinar si el TNF-α-308 está implicado en la susceptibilidad genética, así como las características clínicas y la respuesta terapéutica de EA en la etnia china de Han. Métodos: Se incluyó en el presente estudio a 260 pacientes de EA, y a 260 donantes de sangre sanos y étnicamente equiparables. Se identificó el polimorfismo del promotor de TNF-α-308 mediante amplificación de la reacción en cadena de la polimerasa, con prueba de polimorfismo de longitud de fragmentos de restricción. Resultados: El análisis genético de la población reflejó que la prevalencia del alelo A y el genotipo G/A fue igualmente infrecuente tanto en los pacientes de EA (3,85% y 7,69%) como en los sujetos sanos (4,23% y 8,46%). En comparación con los portadores del genotipo G/G, se observó una tasa de sedimentación eritrocítica y de proteína C reactiva sérica marcadamente elevadas en los pacientes de EA con la variante G/A (87,06±49,4 vs. 55,53±42,99mm/h, p=0,0126; 54,95±27,77 vs. 34,36±36,13mg/dl, p=0,0116, respectivamente), presentándose siempre con dolor vertebral inflamatorio (70 vs. 43,33%, p=0,0214) y sacroilitis relativamente leve (65 vs. 41,67%; p=0,0431). El alelo G y el fenotipo G/G fueron más frecuentes en los pacientes que respondieron bien al tratamiento anti-TNF-α (96,55 vs. 73,53%, p=0,0032; 93,1 vs. 47,06%, p=0,0015), mientras que no se produjo una superioridad obvia de ambos en la predicción de la respuesta terapéutica de las medicaciones convencionales para EA. Conclusiones: Nuestros datos indican que el polimorfismo TNF-α puede influir más en las características clínicas que en la susceptibilidad a EA, en la etnia china de Han (AU)

Background and objective: There is ongoing debate as to whether tumor necrosis factor alpha (TNF-α)-308 is associated with ankylosing spondylitis (AS). The aim of the present study was to determine whether TNF-α-308 is involved into genetic susceptibility, clinical features and therapeutic response of AS in Han Chinese. Methods: Two hundred and sixty AS patients with 260 ethnically matched healthy blood donors were enrolled into the present study. TNF-α-308 promoter polymorphism was identified using polymerase chain reaction amplification with restriction fragment length polymorphism assay. Results: Population genetic analysis showed that the prevalence of allele A and G/A genotype was equally infrequent in both AS patients (3.85% and 7.69%) and healthy subjects (4.23% and 8.46%). Compared with the carriers of G/G genotype, remarkably elevated erythrocyte sedimentation rate and serum C-reactive protein were observed in AS patients with G/A variant (87.06±49.40 vs. 55.53±42.99mm/h, P=.0126; 54.95±27.77 vs. 34.36±36.13mg/dl, P=.0116, respectively), and they always presented with inflammatory spinal pain (70.00% vs. 43.33%, P=0.0214) and suffered relatively mild sacroiliitis (65.00% vs. 41.67%, P=0.0431). The allele G and G/G genotype were more frequent in good responders to anti-TNF-α treatment (96.55% vs. 73.53%, P=.0032; 93.10% vs. 47.06%, P=.0015), whereas there was no obvious superiority of them in predicting therapeutic response of conventional medications for AS. Conclusions: Our data suggest that TNF-α-308 polymorphism may influence the clinical features rather than susceptibility to AS in our Han Chinese (AU)

Ethnicity and disease severity in ankylosing spondylitis a cross-sectional analysis of three ethnic groups.

The purpose of this study is to compare disease severity in ankylosing spondylitis (AS) in three ethnic groups. We assessed 925 AS patients (57 Blacks, 805 Whites, 63 Latinos) enrolled in the longitudinal Prospective Study of Outcomes in AS (PSOAS) for functional impairment, disease activity, and radiographic severity. Comparisons of clinical characteristics and HLA-B27 frequency for each group were performed, in two multivariable regression models, we compared the baseline Bath Ankylosing Spondylitis Radiographic Index (BASRI) and modified Stokes Ankylosing Spondylitis Spine Score (mSASSS) by ethnicity, adjusting for covariates. Blacks had greater functional impairment (Bath Ankylosing Spondylitis Functional Index) (median 62.5 vs. 27.8 in Whites and 38.1 in Latinos; p < 0.0001); higher disease activity (Bath Ankylosing Spondylitis Disease Activity Index), (median 5.9 vs. 3.5 in Whites and 4.5 in Latinos; p < 0.0001), erythrocyte sedimentation rate (median 27.0 in Blacks vs. 10.0 in Whites and 17.0; p < 0.0001), and C-reactive protein levels (median 1.2 vs. 0.4 mg/dL in Whites and 0.9 in Latinos; p < 0.0001). Baseline BASRI and mSASSS were higher in Blacks (mean 9.5 and median 38.2, respectively) compared to Whites (7.3 and 6.4) and Latinos (7.3 and 8.1), (p = 0.004, 0.007), respectively, more significant as disease duration increased. HLA-B27 occurred in 62.5% of Blacks, 85.3% of Whites, and 86.7% of Latinos (p < 0.0001). On multivariable analysis, higher BASRI and mSASSS were associated with Black ethnicity, after adjusting for disease duration and gender as well as TNF inhibitor (TNFi) usage, smoking status, or education level. Blacks with AS have more severe disease compared to either Whites or Latinos.