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.

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.

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.

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.

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.

Genetic diagnostic profiling in axial spondyloarthritis: a real world study.

OBJECTIVES: Spondyloarthritis (SpA) is often diagnosed late in the course of the disease and improved methods for early diagnosis are required. We have tested the ability of genetic profiling to diagnose axial SpA (axSpA) as a whole group, or ankylosing spondylitis (AS) alone, in a cohort of chronic back pain patients. METHODS: 282 patients were recruited from centres in the United Kingdom, Germany, Taiwan, Canada, Columbia and Turkey as part of the ASAS classification criteria for axSpA study (ASAS cohort). Subjects were classified according to the ASAS axSpA criteria, and the modified New York Criteria for AS. Patients were genotyped for ~200,000 immune-mediated disease SNPs using the Illumina Immunochip. RESULTS: We first established the predictive accuracy of genetic data comparing 9,638 healthy controls and 4,428 AS cases from the homogenous International Genetics of AS (IGAS) Consortium Immunochip study which showed excellent predictive power (AUC=0.91). Genetic risk scores had lower predictive power (AUC=0.83) comparing ASAS cohort axSpA cases meeting the ASAS imaging criteria with IGAS controls. Comparing genetic risk scores showed moderate discriminatory capacity between IGAS AS and ASAS imaging positive cases (AUC 0.67±0.05), indicating that significant differences in genetic makeup exist between the cohorts. CONCLUSIONS: In a clinical setting of referred back pain patients suspected to have axial SpA we were unable to use genetic data to construct a predictive model better than that based on existing clinical data. Potential confounding factors include significant heterogeneity in the ASAS cohort, possibly reflecting the disease heterogeneity of axSpA, or differences between centres in ascertainment or classification performance.

Adaptation of Chinese and English versions of the Ankylosing Spondylitis quality of life (ASQoL) scale for use in Singapore.

BACKGROUND: To cross-culturally adapt and validate the Singapore Chinese and Singapore English versions of the Ankylosing Spondylitis Quality of Life (ASQoL) scales. METHODS: Translation of the ASQoL into Singapore Chinese and English was performed by professional and lay translation panels. Field-testing for face and content validity was performed by interviewing ten Chinese speaking and ten English speaking axial spondyloarthritis (AxSpA) patients. AxSpA patients (either Chinese or English speaking) were invited to take part in validation surveys. The Health Assessment Questionnaire (HAQ), Short Form Health Survey (SF-36), Bath Indices, and other measures of disease activity were used as comparator scales for convergent validity. A separate sample of AxSpA patients were invited to participate in a test-retest postal study, with 2 weeks between administrations. RESULTS: The cross-sectional study included 183 patients (77% males, 82% English speaking), with a mean (SD) age of 39.4 (13.7) years. The ASQoL had excellent internal consistency (Cronbach's alpha = 0.88), and correlated moderately with all the comparator scales. The ASQoL was able to distinguish between patients grouped by disease activity and perceived general health. The ASQoL fulfilled the Rasch model analysis for fit, reliability and unidimensionality requirements. No significant differential item functioning was noted for gender, age below or above 50 years, and language of administration. Test-retest reliability was good (r = 0.81). CONCLUSIONS: The ASQoL was adapted into Singapore Chinese and English language versions, and shown to be culturally relevant, valid and reliable when used with combined samples of AxSpA patients who speak either Chinese or English.

CFHR2-rs2986127 as a genetic protective marker for acute anterior uveitis in Chinese patients.

BACKGROUND: Complement factor H (CFH) related proteins (CFHRs) play important roles in complement activation pathways, whereas previous studies have only shown that CFH can affect the development of uveitis. In the present study, we investigated the potential associations between one of single-nucleotide polymorphisms in the CFHR2 gene with acute anterior uveitis (AAU). METHODS: A total of 571 subjects, 283 patients diagnosed with AAU and 288 healthy adult controls, were recruited for this case-control study. CFHR2-rs2986127 was detected using Sequenom MassARRAY technology (Sequenom, San Diego, CA, USA). RESULTS: The stratified analyses for AAU patients with ankylosing spondylitis (AS) revealed a reduced frequency of the A allele in CFHR2-rs2986127 compared to controls (p = 0.033, odds ratio = 0.563, 95% confidence interval = 330-0.960). Further stratified analyses revealed a similar significantly reduced frequency in male AAU patients with AS compared to male controls (p = 0.036, odds ratio = 0.514, 95% confidence interval = 0.274-0.965) and in AAU patients without posterior segment involvement compared to controls (p = 0.048). CONCLUSIONS: The present study reveals an association between CFHR2-rs2986127 and AAU diagnosis, especially with respect to gender, AS status and other clinical signs, such as posterior segment involvement. Our results may further enrich the growing understanding of uveitis genetics, and raise the clinical diagnostic accuracy of this disease. Copyright © 2016 John Wiley & Sons, Ltd.

Associations between vitamin D receptor gene polymorphisms and ankylosing spondylitis in Chinese Han population: a case-control study.

UNLABELLED: We assessed whether the vitamin D receptor gene polymorphisms (FokI, BsmI, ApaI, and TaqI) were associated with ankylosing spondylitis (AS) in a Chinese Han population. The TaqI polymorphism G allele was a risk factor in AS susceptibility. INTRODUCTION: Previous studies have found that serum vitamin D levels are declined in patients with AS. The present study aims to evaluate the role of vitamin D receptor (VDR) gene polymorphisms in AS susceptibility in a Chinese Han population. METHODS: Four single nucleotide polymorphisms (SNPs) in the VDR gene (FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236)) were genotyped by the improved multiplex ligase detection reaction (iMLDR) method in 620 AS patients and 620 geographically and ethnically matched healthy controls. Haplotypes were constructed after linkage disequilibrium (LD) analysis. RESULTS: Statistically significant difference was only found in the TaqI polymorphism between AS patients and controls. The TaqI polymorphism G allele was higher in AS group than that in controls (OR [95 % CI] = 1.624 [1.122-2.352], χ (2) = 6.705, P = 0.006). Linkage disequilibrium has been detected in TaqI and BsmI polymorphisms (D' = 0.87, r (2) = 0.70). Two novel haplotypes (H1: AC and H2: GT) were significantly associated with the risk of AS, and they play protective and risk roles in AS morbidity, respectively. CONCLUSIONS: The VDR gene TaqI polymorphism G allele may be a risk factor in AS susceptibility.

Comparison on radiographic progression for 5 years between juvenile onset ankylosing spondylitis and adult onset ankylosing spondylitis: an observational study of the Korean SpondyloArthropathy Registry (OSKAR) data.

OBJECTIVES: To evaluate differences in radiographic progression between adult-onset ankylosing spondylitis (AoAS) and juvenile-onset ankylosing spondylitis (JoAS). METHODS: A total of 533 patients (418 patients with AoAS and 115 patients with JoAS) from the Observation Study of Korean spondyloArthropathy Registry (OSKAR) cohort were enrolled. All baseline OSKAR data were analysed in relation to disease onset and radiographic progression was analysed between the groups over 5 years. The modified Stoke AS Spinal Score (mSASSS) were used by two experienced radiologists. Clinical data were collected to investigate the associations between clinical factors and radiographic progression. Radiographic scores were compared using analysis of covariance model after adjusting for confounding factors. RESULTS: Inter-reader reliability for baseline mSASSS was very good. Inter-reader reliability for the changes in the mSASSS was also good. A significant difference in baseline mSASSS (mean ± SD) unit was detected between the AoAS and JoAS groups (18.1±17.4 vs. 14.3±13.8, p=0.015). We assessed the change in mSASSS to confirm whether age at onset affected radiographic progression. A simple comparison revealed a significant difference between changes on the mSASSS (mean ± SEM) between the JoAS and AoAS groups (1.75±0.71 vs. 3.77±0.56, p<0.001). After adjusting for multiple comparisons, change on the mSASSS remained lower in patients with JoAS than those with AoAS (0.28±1.33 vs. 4.08±0.62, p=0.016). CONCLUSIONS: Patients with JoAS had slower radiographic spinal damage progression over 5 years than those with AoAS.

Association study of copy number variants in FCGR3A and FCGR3B gene with risk of ankylosing spondylitis in a Chinese population.

Ankylosing spondylitis (AS) is a common inherited autoimmune disease. Copy number variation (CNV) of DNA segments has been found to be an important part of genetic variation, and the FCGR3A and FCGR3B gene CNVs have been associated with various autoimmune disorders. The aim of the study was to determine whether CNVs of FCGR3A and FCGR3B were also associated with the susceptibility of AS. A total of 801 individuals including 402 AS patients and 399 healthy controls were enrolled in this study. The copy numbers of FCGR3 gene (two fragments, included FCGR3A and FCGR3B) were measured by AccuCopy™ methods. Chi-square test and logistic regression model were used to evaluate association between FCGR3 gene CNVs and AS susceptibility. P values, odds ratio, and 95% confidence intervals (CIs) were used to estimate the effects of risk. Significantly, difference in the frequencies of FCGR3A and FCGR3B gene CNVs was founded between the patients with AS and controls. For the FCGR3A gene, a low (≤3) copy number was significantly associated with AS [for ≤3 copies versus 4 copies, (OR 2.17, 95% CI (1.41, 3.34), P < 0.001, adjusted OR 2.22, 95% CI (1.44, 3.43), P < 0.001)]. A low FCGR3B copy number was also significantly associated with increasing risk of AS [for ≤3 copies versus 4 copies, (OR 1.87, 95% CI (1.25, 2.79), P = 0.002, adjusted OR 1.94, 95% CI (1.29, 2.91), P = 0.001)]; however, both the high FCGR3A and FCGR3B copy numbers (≥5) were not significantly associated with the risk of AS (≥5 copies versus 4 copies). The lower copy numbers (≤3) of FCGR3A and FCGR3B genes confer a risk factor for AS susceptibility.

Association study of ankylosing spondylitis and polymorphisms in ERAP1 gene in Zhejiang Han Chinese population.

The susceptibility loci of ERAP1 polymorphisms have been found to be strongly associated with ankylosing spondylitis (AS). The researches in multiple ethnic cohorts suggested that the population attributable risk in ERAP1 polymorphisms is at a high significance level. This study was undertaken to estimate the prevalence and incidence of subsets of AS and investigate the specific variants of ERAP1 polymorphisms in AS susceptibility, in the Han ethnic Chinese population in Zhejiang Province. AS patients were selected, diagnosed, and confirmed by a qualified rheumatologist. The basal clinical and demographic characteristics were compared with all subjects. Genotypes for eight selected single nucleotide polymorphisms (SNPs) in ERAP1 gene (rs27038, rs27037, rs27434, rs27980, rs7711564, rs30187, rs10050860, and rs17482078) were determined by using the Sequenom MassARRAY iPLEX platform in Zhejiang Han Chinese population. Association analyses were performed on the whole genotyped data set in 707 unrelated ankylosing spondylitis cases and 837 ethnically matched controls. We observed the strongest association between AS and HLA-B27, which confers over 90 % of ankylosing spondylitis cases. Moreover, we found three loci of ERAP1 polymorphisms were at a high significance level (rs27037 P = 0.00451; rs27434 P = 0.00012; rs27980 P = 0.00682) with AS in Zhejiang population. We also confirmed polymorphism locus of ERAP1 previously reported association with AS (rs27434; P = 5.3 × 10(-12)). Our results indicated a difference in the mechanism of susceptibility loci in subsets of Zhejiang Han Chinese population and provided further evidence that rs27434 is the key polymorphism associated with AS in ERAP1 gene.

Cross-cultural adaptation and validation of the Portuguese version of "The assessment of knowledge in ankylosing spondylitis patients by a self-administered questionnaire".

Knowledge is an important factor in patients with ankylosing spondylitis regarding the adoption of appropriate behaviours and education. The aim of this study was to culturally adapt and validate "The assessment of knowledge in ankylosing spondylitis patients by a self-administered questionnaire" for the Portuguese population with ankylosing spondylitis. The Portuguese version of "The assessment of knowledge in ankylosing spondylitis patients by a self-administered questionnaire" was administered to a sample of 180 subjects, from which 63 individuals responded. The adaptation process involved translation, back-translation and submission to a committee of experts in the area, culminating with a Portuguese version of the instrument. Next, the scale reliability and validity were assessed. There was a statistically significant decrease from test to retest, although the intra-class correlation coefficient between test and retest was 0.76 (95 % CI 0.61-0.86), which was considered good. From 180 individuals, 63 (35.0 %) subjects were available for the present study. The proportion of individuals that correctly answered each item ranged from 19 to 92 %, corresponding to items 8 and 13, respectively. The mean number of correct answers was 8.5 [mean (SD) = 2.4] in 12 questions. The proposed Portuguese version of the ankylosing spondylitis knowledge scale showed good reliability, reproducibility and construct validity.

Determination of IL1 R2, ANTXR2, CARD9, and SNAPC4 single nucleotide polymorphisms in Iranian patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin, while both genetic and environmental factors have been demonstrated to be etiologically involved. Recent genome-wide association and replication studies have suggested that anthrax toxin receptor 2 (ANTXR2), interleukin-1 receptor 2 (IL1R2), caspase recruitment domain-containing protein 9 (CARD9), and small nuclear RNA-activating complex polypeptide 4 (SNAPC4) seem to be associated with AS pathogenesis. This case-control study was performed on 349 unrelated AS patients and 469 age- and gender-matched healthy controls, to investigate whether these non-MHC genes (IL1R2 rs2310173, ANTXR2 rs4333130, CARD9 rs4077515, and SNAPC4 rs3812571) influence the AS risk in Iranian population. ANTXR2 rs4333130 allele C (p = 0.0328; OR 0.744, 95% CI 0.598-0.927) and genotype CC (p = 0.0108; OR 0.273, 95% CI 0.123-0.605) were found to be significantly protective against AS. No other associations were found between AS and studied genes. The association between ANTXR2 rs4333130 and AS was independent of HLA-B27 status. Moreover, we found clinical disease severity scores (BASDAI and BASFI) and pain score were higher in ANTXR2 rs4333130 CT genotype. However, we observed that CARD9 allele C (p = 0.012) and genotype CC (p = 0.012) were significant protective factors against AS only in HLA-B27-negative patients, and IL1R2 rs2310173 genotype GT was mildly protective against AS only in HLA-B27-negative status. These findings support the role of non-MHC pathogenic pathways in susceptibility to AS and warrants more comprehensive studies focusing on these non-MHC pathways for developing novel therapeutic strategies.

The clinical usefulness of ESR, CRP, and disease duration in ankylosing spondylitis: the product of these acute-phase reactants and disease duration is associated with patient's poor physical mobility.

We evaluated the clinical usefulness of ESR, CRP, and disease duration in ankylosing spondylitis (AS) disease severity. There were 156 Chinese AS patients included in Taiwan. Patients completed the questionnaires, containing demographic data, disease activity (BASDAI), functional status (BASFI), and patient's global assessment (BASG). Meanwhile, patient's physical mobility (BASMI) and acute-phase reactants, including ESR and CRP levels were measured. Receiver operating characteristic (ROC) plot analysis was used to evaluate the performance of ESR, CRP, and disease duration in the AS patients. ESR mildly correlated with BASFI (r = 0.176, p = 0.028) and disease duration (r = 0.214, p = 0.008), and moderately correlated with BASMI (r = 0.427, p < 0.001). CRP moderately correlated with BASMI (r = 0.410, p < 0.001). By using ROC plot analysis, ESR, CRP, and disease duration showed the best and significant "area under the curve (AUC)", in distinguishing the AS patients with poor physical mobility (BASMI ≥ 3.6, the Median) (AUC = 0.748, 0.751 and 0.738, respectively, all p < 0.001), as compared to BASDAI, BASFI, and BASG. ESR × disease duration (AUC = 0.801, p < 0.001) and CRP × disease duration (AUC = 0.821, p < 0.001) showed higher AUC values than ESR or CRP alone in indicating poor physical mobility. For detecting poor physical mobility (BASMI ≥ 3.6) in the AS patients: ESR × disease duration (≥60.0 mm/h × year): sensitivity = 72.7 % and specificity = 72.8 %; CRP × disease duration (≥8.3 mg/dl × year): sensitivity = 72.7 % and specificity = 74.6 %. ESR, CRP, and disease duration are particularly related to AS patient's poor physical mobility. Combining the usefulness of acute-phase reactants and disease duration, the values of ESR × disease duration and CRP × disease duration demonstrate better association with poor physical mobility in AS patients.

Raised incidence of ankylosing spondylitis among Inuit populations could be due to high HLA-B27 association and starch consumption.

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis mainly affecting the spinal joints. It would appear that the most likely causative agent in the development of AS is an environmental factor in the genetically susceptible, HLA-B27 positive, individuals. Extensive data from several countries support the notion that Klebsiella pneumonia bacteria are the most likely culprit in the causation of AS. These microbes possess antigens which resemble HLA-B27 and spinal collagens. Increased intake of high-starch diet is directly proportional to the gut-associated bacterial load, especially in the large intestine, and among these microbial agents, Klebsiella is considered as one of the main constituting components. Therefore, a low-starch diet intake alongside the currently used medical therapeutic modalities could be beneficial in the management of patients with early AS. It is suggested that a change in the dietary habits from high protein, low-starch marine components to the Westernized high-starch diet among the Inuit peoples of Alaska and Canada could be considered as one of the main contributing factors in the increased prevalence of AS during the last few decades within this genetically unmixed native population.

Prevalence of HLA-B27 in Moroccan healthy subjects and patients with ankylosing spondylitis and mapping construction of several factors influencing AS diagnosis by using multiple correspondence analysis.

The aim of the present study was to determine the prevalence of human leukocyte antigen HLA-B27 in Moroccan healthy controls and in patients with ankylosing spondylitis (AS), and to analyze the correlation between HLA-B27 and AS in Moroccan patients. The prevalence of HLA-B27 was determined by evaluating the number of HLA-B27-positive samples in 128 healthy subjects and in 53 patients diagnosed with AS according to the ESSG and AMOR criteria. HLA-B27 was determined by the polymerase chain reaction using sequence-specific primers. Multivariate analysis of our data (HLA-B27, age, sex, and family history) for AS and healthy controls was performed by multiple correspondence analysis (MCA). The frequency of HLA-B27 was significantly greater in AS patients (45.3 %) than in healthy controls (4.7 %) [p < 0.0001, OR 16.8, and CI 95 % (5.83-51.03)]. In addition, HLA-B27 was more common in male patients than in female ones (p < 0.05). 100 % of the AS patients reported a family history of AS, whereas only 20 % of the healthy controls reported a family history of AS. The graphical interpretation of MCA showed a significant relation between the presence of HLA-B27 and AS. This study strengthens the link between HLA-B27 and AS and represents a very valuable informative diagnostic tool, especially in regard to male patients who have a family history of AS.

Meta-analysis of genetic polymorphisms in programmed cell death 1. Associations with rheumatoid arthritis, ankylosing spondylitis, and type 1 diabetes susceptibility.

OBJECTIVE: The aim of this study was to determine whether genetic polymorphisms in programmed cell death 1 (PDCD1 or PD1) are associated with susceptibility to rheumatoid arthritis (RA), ankylosing spondylitis (AS), and type 1 diabetes (T1D). METHODS: We conducted a meta-analysis to investigate the association between PDCD1 polymorphisms and RA, AS, and T1D in the overall population and in specific ethnic populations. RESULTS: Sixteen studies, comprising 13,210 patients and 17,073 controls, were conducted for the meta-analysis including 4 studies on RA, 4 on AS, and 8 on T1D. The meta-analysis showed an association between RA and the 2 alleles of the PD1.3 polymorphism in the overall population [odds ratio (OR) 1.183, 95 % confidence interval (95 % CI) 1.005-1.392, p = 0.043]. However, meta-analysis showed no association between RA and the 2 alleles of the PD1.1 and PD1.5 polymorphisms in the overall population. Meta-analysis identified an association between AS and the 2 alleles of the PD1.5 and PD1.9 polymorphisms in the Asian population (OR 1.251, 95 % CI 1.019-1.535, p = 0.033; OR 1.975, 95 % CI 1.286-3.034, p = 0.002, respectively). The meta-analysis revealed a significant association between T1D and the 2 alleles of the PD1.3 polymorphism in the European population (OR 1.098, 95 % CI 1.029-1.171, p = 0.005). The meta-analysis showed an association between the PD1.5 polymorphism and T1D in Asians (OR 1.332, 95 % CI 1.067-1.663, p = 0.011) and between the PD1.9 polymorphism and T1D in the Asian population (OR 1.363, 95 % CI 1.107-1.679, p = 0.004). CONCLUSION: The meta-analysis suggests an association between the PD1.3 polymorphism and RA in the overall population and an association between the PD1.5 and PD1.9 polymorphisms, and AS in the Asian population. Furthermore, the PD1.3 , 5, and 9 polymorphisms were associated with T1D susceptibility in Europeans, or Asians.

Association of HLA-B27 and ERAP1 with ankylosing spondylitis susceptibility in Beijing Han Chinese.

This study investigated the genetic polymorphisms of HLA-B27, together with polymorphisms on endoplasmic reticulum aminopeptidase 1 (ERAP1), and susceptibility for ankylosing spondylitis (AS) in the Beijing Han population. A case-control study was carried out for 602 AS patient samples and 619 matched controls of Han Chinese. HLA-B27 genotyping was performed by polymerase chain reaction-sequence specific primers (PCR-SSP), and four ERAP1 SNPs (rs27037, rs27980, rs27582, and rs27434) were selected and genotyped on the Sequenom iPlex platform (Sequenom, San Diego, CA). Association analysis was performed using the likelihood ratio χ(2) test. This study identified four HLA-B27 alleles in Beijing Han AS patients, B*27:02, B*27:04, B*27:05, and B*27:07, of which B*27:05 was the most significant geographical different subtype among AS patients in Chinese. Our results confirmed that HLA-B27 was strongly associated with AS (P=1.9 × 10(-150) ), and the most strongly associated alleles were B*27:04, B*27:05, and B*27:02. Our study also confirmed a weak association between ERAP1 (rs27434) and AS. We also observed that for HLA-B*27:02 and HLA-B*27:04 positive AS patients, rs27434 and rs27582 were associated with AS. In contrast, for HLA-B27-negative and HLA-B*27:05-positive AS patients, this association was not observed. This is the first study to show that both B27 and ERAP1 are AS genetic susceptibility genes in Beijing Han. Interactions between ERAP1 and HLA-B*27:02 and B*27:04 may play an important role in the AS pathogenesis.

MICA, a gene contributing strong susceptibility to ankylosing spondylitis.

OBJECTIVE: The human major histocompatibility complex class I chain-related gene A (MICA) controls the immune process by balancing activities of  natural killer cells, γδ T cells and αß CD8 T cells, and immunosuppressive CD4 T cells. MICA is located near HLA-B on chromosome 6. Recent genomewide association studies indicate that genes most strongly linked to ankylosing spondylitis (AS) susceptibility come from the region containing HLA-B and MICA. While HLA-B27 is a well-known risk genetic marker for AS, the potential effect of linkage disequilibrium (LD) shields any associations of genes around HLA-B with AS. The aim of this study was to investigate a novel independent genetic association of MICA to AS. METHODS: We examined 1543 AS patients and 1539 controls from two ethnic populations by sequencing MICA and genotyping HLA-B alleles. Initially, 1070 AS patients and 1003 controls of European ancestry were used as a discovery cohort, followed by a confirmation cohort of 473 Han Chinese AS patients and 536 controls. We performed a stratified analysis based on HLA-B27 carrier status. We also conducted logistic regression with a formal interaction term. RESULTS: Sequencing of MICA identified that MICA*007:01 is a significant risk allele for AS in both Caucasian and Han Chinese populations, and that MICA*019 is a major risk allele in Chinese AS patients. Conditional analysis of MICA alleles on HLA-B27 that unshielded LD effect confirmed associations of the MICA alleles with AS. CONCLUSIONS: Parallel with HLA-B27, MICA confers strong susceptibility to AS in US white and Han Chinese populations.