Ankylosing Spondylitis Susceptibility Research Articles

Functional ERAP1 Variants Distinctively Associate with Ankylosing Spondylitis Susceptibility under the Influence of HLA-B27 in Taiwanese

Epistasis of ERAP1 single nucleotide variations (SNVs) and HLA-B27 has been linked to ankylosing spondylitis susceptibility (AS). The current study examined how prevalent ERAP1 allelic variants (SNV haplotypes) in Taiwan affect ERAP1 functions and AS susceptibility in the presence or absence of HLA-B27. Sanger sequencing was used to discover all ERAP1 coding SNVs and common allelic variants in Taiwanese full-length cDNAs from 45 human patients. For the genetic association investigation, TaqMan genotyping assays were utilized to establish the genotypes of ERAP1 SNVs in 863 AS patients and 1438 healthy controls. Ex vivo biological analysis of peripheral blood mononuclear cells from homozygous donors of two common-risk ERAP1 allelic variants was performed. Two common-risk ERAP1 allelic variants were also cloned and functionally studied. In Taiwanese, eleven frequent ERAP1 SNVs and six major ERAP1 allelic variants were discovered. We discovered that in Taiwanese, the most prevalent ERAP1-001 variant with 56E, 127R, 276I, 349M, 528K, 575D, 725R, and 730Q interacting with HLA-B27 significantly contributed to the development of AS. In HLA-B27 negative group, however, the second most prevalent ERAP1-002 variant with 56E, 127P, 276M, 349M, 528R, 575D, 725R, and 730E was substantially related with an increased risk of AS. Ex vivo and in vitro research demonstrated that ERAP1 allelic variants have a significant impact on ERAP1 functions, suggesting that ERAP1 plays a role in the development of AS. In an HLA-B27-dependent manner, common ERAP1 allelic variants are related with AS susceptibility.

Genetic effects of B3GNT2 on ankylosing spondylitis susceptibility and clinical manifestations in Taiwanese

The intergenic SNP rs10865331 at 2p15 was identified as a major risk factor for ankylosing spondylitis (AS) susceptibility in genome-wide association studies (GWAS). B3GNT2 gene regulates polylactosamine synthesis is potentially functionally relevant to AS disease development. We investigated whether SNP rs10865331 and two B3GNT2 SNPs (rs11900673 and rs1136151) are associated with AS susceptibility and disease severity in Taiwanese. Distributions of genotypes, alleles, and haplotypes of three SNPs were compared between 1,472 AS patients and 2,117 healthy blood donors and among AS patients stratified by clinical characteristics. The intergenic SNP rs10865331 was significantly associated with AS (PFDR=1.02E-05) in Taiwanese. In AS patients stratified by positivity of HLA-B27 and syndesmophyte formation, all three B3GNT2 locus SNPs (rs11900673, rs1136151, and rs10865331) were significantly associated with syndesmophyte formation among HLA-B27 positive AS patients. Haplotype analyses revealed that the "CTA" (rs11900673C/rs1136151T/rs10865331A) haplotype was significantly associated with AS susceptibility (Padj=0.0177) and syndesmophyte formation (Padj=0.016) in HLA-B27 positive patients. In contrast, "TCG" (rs11900673T/rs1136151C/rs10865331G) haplotype showed protection against AS development (Padj=0.0005 for HLA-B27 positive and Padj=0.004 for HLA-B27 negative, respectively) and syndesmophyte formation (Padj=0.0017) in HLA-B27 positive patients. Furthermore, B3GNT2 mRNA expressions were negatively associated with erythrocyte sedimentation rate (ESR, P=0.0103), C-reactive protein (CRP, P=0.0353), Bath ankylosing spondylitis functional index (BASFI, P=0.0171), and syndesmophyte formation (P=0.0148). Our data suggest that B3GNT2 gene may contribute to AS development and affect AS severity by interacting with HLA-B27 in Taiwanese.

Lack of association between TNF polymorphism and ankylosing spondylitis susceptibility in HLA-B27-positive population: a meta-analysis.

Human leukocyte antigen (HLA)-B27 plays a crucial role in the pathogenesis of AS. TNF polymorphisms have been reported to be associated with AS susceptibility, but the results of these previous studies have been inconsistent. The aim of this study was to explore whether TNF polymorphism is associated with AS susceptibility in HLA-27-positive population. Our search was done in the Pubmed, Embase, and Cochrane databases (up to March 2020). The pooled and individual odds ratios (ORs) with 95% confidence intervals (CIs) of the minor allele of each locus were presented to assess the associations between TNF polymorphisms and AS in HLA-B27-positive population. Ten studies from 8 articles were included in this meta-analysis. In the population of HLA-B27-positive patients and random healthy controls, there were statistical significance in the evaluation of association between the minor allele of TNF-238, -308, -857, -1031 and -863 and AS susceptibility, respectively. In the population of HLA-B27-positive patients and HLA-B27-positive healthy controls, there were no statistical differences in the comparison of minor allele of with their respective major allele in the fixed model. There was no association of the TNF polymorphisms with AS in the HLA-B27-positive AS group and HLA-B27-positive control group. Polymorphisms of TNF-238, -308, -857, -1031, -863 were associated with AS susceptibility in the HLA-B27-positive AS patients and random control population. Other gene SNPs except TNF may play an important role in AS susceptibility in HLA-B27-positive population.

The association of polymorphisms in TNF and ankylosing spondylitis in common population: a meta-analysis.

Studies investigating the association between the polymorphisms in TNF and ankylosing spondylitis have been reported the conflicting results. Here we performed a meta-analysis based on the evidence available from the literature up-to-date to further clarify this relationship. Our systematic search was done in the PubMed, Embase and Cochrane databases (up to March 2020). The pooled and individual odds ratios (ORs) with 95% confidence intervals (CIs) of the minor allele of each locus were presented to assess the associations between TNF polymorphisms and AS in different ethnicities in common population. Seventeen studies, consisting of seven European studies, eight East Asian studies and two Latin-American studies, were included in this meta-analysis. In the total population, the A allele in TNF-238 (OR = 0.702, 95%CI = 0.506-0.973, p = 0.034) and TNF-308 (OR = 0.638, 95%CI = 0.507-0.804, p = 0.000), the C allele in TNF-1031 (OR = 0.594, 95%CI = 0.446-0.791, p = 0.000), the T allele in TNF-850 (OR = 3.462, 95%CI = 1.764-6.798, p = 0.000) and rs769178 (OR = 2.593, 95%CI = 2.175-3.091, p = 0.000) were significantly associated with AS susceptibility. There were no significant association between the minor alleles of TNF-376, TNF-857, TNF-863 and AS susceptibility. There are inconsistent results in the Latin-American population and East Asian population with those in the total population. Our meta-analysis suggests that TNF-α polymorphisms at positions - 238, - 308, - 850, - 1031 and rs769178 could have an influence on ankylosing spondylitis susceptibility in the total population. But there is no association of the TNF-376, TNF-857, TNF-863 polymorphisms with ankylosing spondylitis. Some results in the subgroups are not consistent with those in the total population.

Associations of Tumor Necrosis Factor Alpha Gene Polymorphisms and Ankylosing Spondylitis Susceptibility: A Meta-analysis Based on 35 Case-control Studies

ABSTRACT Background Scores of studies on tumor necrosis factor alpha (TNF-α) gene polymorphisms and AS have been performed with inconsistent results. The purpose of this study was to provide some more convincing evidence on the associations of TNF-a polymorphisms and AS by using a meta-analysis approach. Methods Potentially relevant studies were identified from Web of Science, PubMed, EMBASE, Wanfang, and CNKI from inception to March 5, 2020. Newcastle–Ottawa Scale (NOS) was utilized to appraise the quality of included studies. Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to assess the strength of the associations under five genetic models. Results Thirty-five studies with 37 independent cohorts in total were included in the meta-analysis. Based upon NOS, eligible studies were in moderate- to high quality. The merged data suggested rs1799724 polymorphisms were significantly correlated with a reduced risk of AS (C vs. T, OR = 0.55, 95%CI 0.38–0.79, P < .001, PBon = 0.005, PFDR = 0.003). Subgroup analysis by ethnicity indicated that rs1800629 polymorphism significantly increased the risk of AS in Caucasians and decreased the risk of AS in mixed populations. Besides, rs361525 and rs1800630 polymorphisms conferred to an elevated risk of AS, and rs1799724 conferred to a reduced risk of AS in Asians. Conclusions This study suggests that rs1800629 polymorphism is associated with an increased AS risk in Caucasians, rs361525 and rs1800630 polymorphisms are linked to an elevated AS susceptibility in Asians.

Connection of COX-2 variants to ankylosing spondylitis susceptibility.

This study aimed to explore the associations of COX-2 polymorphisms rs5275, rs20417, and rs2745557 with the susceptibility to ankylosing spondylitis among Chinese Han people. Polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) was adopted for genotyping COX-2 polymorphisms rs5275, rs20417, and rs2745557 among 109 AS patients and 122 healthy controls. Genotype distribution in the control group was examined for these three polymorphisms to test whether it conformed to Hardy-Weinberg equilibrium (HWE) expectation. A χ2 -test was employed to compare genotype and allele frequencies between the two groups. Besides this, logistic regression analyses were also performed to adjust age and gender. Apless than .05 represented a significant level. Genotype distribution of our studied polymorphisms showed fine conformity to HWE in the controls. An increasing effect on AS risk was detected for the polymorphism rs5275 under GG versus AA contrast (crude: OR,3.040; 95% CI,1.015-9.104), and the adjustment for age and gender did not change such a relationship (adjusted OR,3.307; 95% CI,1.065-10.268). After adjusting age and gender, both polymorphisms of rs20417 and rs2745557 demonstrated a negative relationship with the disease susceptibility. The GC genotype and C allele of rs20417 reduced the disease risk to 0.248 (adjusted: 95% CI,0.089-0.692) and 0.269 (95% CI,0.098-0.733), respectively, while the AA genotype and A allele of the latter to 0.413 (adjusted: 95% CI,0.191-0.893) and 0.676 (adjusted: 95% CI,0.466-0.981), respectively. Among Chinese Han people, COX-2 polymorphism rs5275 may contribute to increased risk of developing AS, while the polymorphisms rs20417 and rs2745557 may offer protection against disease incidence.

Association of the genetic variants in the endoplasmic reticulum aminopeptidase 2 gene with ankylosing spondylitis susceptibility.

Genetic polymorphisms in the endoplasmic reticulum aminopeptidase gene ERAP2 has been attributed with the etiopathogenesis of ankylosing spondylitis (AS). Here we assessed the association of ERAP2 gene single nucleotide polymorphisms (SNPs) with AS predisposition in Iranian patients and determined their effect on the inflammatory state of the patients. For genotyping of rs2548538, rs2287988, and rs17408150 SNPs using a real-time allelic discrimination approach, DNA was extracted from the whole blood of 250 AS patients and 250 healthy individuals. RNA of the peripheral blood mononuclear cells was separated, cDNA was synthesized, and transcriptional levels of cytokines, including interleukin (IL)-17A, IL-23, IL-10, and transforming growth factor-β, were measured. Enzyme-linked immunosorbent assay was used to measure the serum concentration on the cytokines. Three ERAP2 gene SNPs were not associated significantly with AS risk. Nonetheless, rs2287988 and rs17408150 SNPs showed statistically significant association with susceptibility to the disease in those AS patients who were positive for human leukocyte antigen (HLA)-B27. Transcriptional level and serum concentration of IL-17A and IL-23 were higher, but those of IL-10 were lower in both AS patients and the HLA-B27-positive patient group relative to the control group. Nevertheless, ERAP2 gene SNPs in the HLA-B27-positive AS patients did not affect the transcription level and serum concentration of cytokines. ERAP2 gene rs2287988 and rs17408150 SNPs are associated with susceptibility to AS, but they are probably not determining the levels of IL-17A, IL-23, and IL-10 in this disease.

The rs6427384 and rs6692977 Single Nucleotide Polymorphisms of the Fc Receptor-Like 5 (FCRL5) Gene and the Risk of Ankylosing Spondylitis: A Case Control Study in a Single Center in China.

BackgroundThe study aimed to explore the genetic association of Fc receptor-like 5 (FCRL5) gene variants (rs6427384 and rs6692977) with ankylosing spondylitis risk in Chinese Han population.Material/MethodsGenotyping for FCRL5 gene variations rs6427384 and rs6692977 was implemented among 130 ankylosing spondylitis cases and 135 healthy persons, through polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Frequency dissimilarity for 2 polymorphisms was compared between 2 groups using chi-square test. The association strength of FCRL5 gene polymorphism with ankylosing spondylitis risk was estimated by odds ratios with 95% confidence intervals.ResultsThe frequencies of rs6427384 CC genotype and C allele were significantly lower in the case group than that in the control group (P<0.05), which suggested that C allele of rs6427384 polymorphism might offer protection against ankylosing spondylitis onset. Whereas only 2 genotypes of rs6692977 were detected in the control group, and no significant association was found with ankylosing spondylitis susceptibility.ConclusionsFCRL5 gene polymorphism rs6427384 was correlated to ankylosing spondylitis occurrence among Chinese Han population, while rs6692977 was not.

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/β-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/β-catenin signalling pathway for understanding the genetic architecture of AS.

Analysis of 47 Non-MHC Ankylosing Spondylitis Susceptibility Loci Regarding Associated Variants across Whites and Han Chinese.

To present a systematic evaluation of 47 non-MHC ankylosing spondylitis (AS) susceptibility loci that have been initially discovered through white genome-wide association studies in Han Chinese. Originally, 10,743 samples representing north and south Chinese in 4 datasets were obtained. After data quality control and imputation, metaanalysis results of 94,621 variants within 47 loci were extracted. Four ERAP1 single-nucleotide polymorphisms (SNP) and HLA-B27 tag SNP rs13202464 were used for interaction analysis. Population-attributable risk percentages of AS-associated variants were compared. Functional annotations of AS-associated variants were conducted using HaploReg, RegulomeDB, and rVarBase databases. We revealed 16 AS-associated variants with nominal evidence in Han Chinese, including rs10865331 (p = 6.30 × 10-10), rs10050860 (p = 4.09 × 10-5) and rs8070463 (p = 1.03 × 10-4). Potential susceptible SNP within these 47 loci were also identified, such as rs13024541 (2p15), rs17401719 (5q15), and rs62074054 (17q21). Epistatic interactions between 3 ERAP1 SNP (rs17401719, rs30187, and rs10050860) and HLA-B27 were confirmed. Among the 16 AS-associated variants, rs30187 showed weaker risk effect, while rs10050860 and rs12504282 seemed to attribute more risk in Han Chinese than in whites. Further genomic annotation pinpointed 35 candidate functional SNP, especially in the 2p15, ERAP1, and NPEPPS-TBKBP1 regions. Our results provided a detailed spectrum of all the reported non-MHC AS susceptibility loci in Han Chinese, which comprehensively exhibited the ethnic heterogeneity of AS susceptibility and highlighted that 2p15, ERAP1, and NPEPPS-TBKBP1 regions may play a critical role in AS pathogenesis across diverse populations.

TIMP3 gene polymorphisms and relation to Ankylosing spondylitis susceptibility in Chinese Han population.

Ankylosing spondylitis (AS) is a type of chronic progressive inflammatory disease, which often causes significant damage to the patients on the physical function, labour ability and quality of life. The study found that the enzyme system tissue inhibitor of matrix metalloproteinases (TIMPs) was important for the development of AS. The aim of this study was to investigate the association of polymorphisms of TIMP3 gene with AS in Chinese Han population. To evaluate the correlation of TIMP3 polymorphisms with AS risk, Agena MassARRAY was used to determine the genotypes of 268 AS patients and 654 controls. The correlation between TIMP3 variants and AS risk was examined by unconditional logistic regression analysis. Haplotype construction and analysis in TIMP3 were also applied to detect the potential association. We identified that rs11547635 in the TIMP3 gene (odds ratio[OR]=0.79, 95% confidence intervals [CI]: 0.63-0.98, p=.029) was significantly associated with a decreased risk of AS in the alleles model.Rs715572 AG genotype (OR=1.57, 95% CI: 1.05-2.34, p=.041) was potentially associated with an increased risk of AS, and also rs715572 in the dominant model (OR=1.61, 95% CI: 1.10-2.36, p=.013) and log-additive model (OR=1.41, 95% CI: 1.07-1.86, p=.016) adjusted by age and gender were significantly correlated with an increased AS risk. These findings suggested that polymorphisms of the TIMP3 gene may be associated with susceptibility to AS.

Association study between matrix metalloproteinase-3 gene (MMP3) polymorphisms and ankylosing spondylitis susceptibility.

BackgroundAnkylosing spondylitis (AS) is the second most common cause of inflammatory arthritis worldwide affecting the axial skeleton. Single nucleotide polymorphisms (SNPs) of matrix metalloproteinase‐3 (MMP3) in the development of AS has few been investigated in Chinese population.MethodsA total of 362 patients with AS and 362 healthy controls were enrolled in the study. Five SNPs in MMP3 genotypes were identified by Agena MassARRAY. Chi‐squared tests and genetic model were used to evaluate associations.Resultsrs522616 had a significant risk of AS development compared to those with the TT genotype (p = 0.008). By multiple logistic regression models analysis, in codominant model, rs522616 CT genotypes also had a 1.44‐fold risk (95% CI = 1.06–1.96, p = 0.008) for AS development compared to those with TT genotypes. In recessive model, the CC genotypes was a significantly reduced AS risk for individuals with TT/CT genotype (OR = 0.64; 95% CI = 0.41–0.99, p = 0.040).ConclusionThe present study suggests that MMP3 rs522616 polymorphism is associated with AS susceptibility and MMP3 might be a potential diagnostic biomarker for AS. Further independent studies with larger cohorts are warranted to validate our findings in different populations.

Association between cytokine gene polymorphisms and ankylosing spondylitis susceptibility: a systematic review and meta-analysis

Purpose of the studyThe aim of this study was to perform a meta-analysis to derive precise estimation of the association of interleukin-23 receptor (IL-23R), IL-1 receptor 2 (IL-1R2), IL-12 beta...

Associations between interleukin-23R polymorphisms and ankylosing spondylitis susceptibility: an updated meta-analysis.

The aim of this study was to determine whether interleukin-23R (IL-23R) polymorphisms are associated with susceptibility to ankylosing spondylitis (AS). Meta-analyses were conducted to determine the associations between IL-23R polymorphisms and AS susceptibility in Europeans, Asians, and all subjects combined. Atotal of 17studies (21separate comparisons) were included in this meta-analysis. The meta-analysis revealed asignificant association between AS and the two alleles of the rs11209032 polymorphism in all study subjects (odds ratio [OR] = 1.160, 95% confidence interval [CI] = 1.091-1.204, P < 0.001). Stratification by ethnicity identified asignificant association between this polymorphism and AS in Europeans (OR = 1.234, 95% CI = 1.159-1.313, P < 0.001), but not in Asians (OR = 1.003, 95% CI = 0.920-1.219, P = 0.942). Meta-analyses of the rs1004819, rs10489629, rs1343151, rs1495965, rs7517847, and rs11465804 polymorphisms showed the same pattern as shown for rs11209032. The meta-analysis also revealed asignificant association between the two alleles of the rs2201841 and rs11209026 polymorphisms and the risk of developing AS in Europeans, but not in Asians. Interestingly, the rs10889677 polymorphism was not found to be associated with AS susceptibility in either Europeans or Asians. This meta-analysis showed that several IL-23R polymorphisms are associated with the development of AS in Europeans.

Association of the HLA-B27 antigen and the CTLA4 gene CT60/rs3087243 polymorphism with ankylosing spondylitis in Algerian population: A case-control study.

Ankylosing spondylitis (AS) is a complex inflammatory disease that represents a major health problem both in Algeria and worldwide. Several lines of evidence support that genetic risk factors play a role in AS etiology and the CTLA4 gene has attracted a considerable attention. In this study, we were interested in evaluating the HLA-B27 frequency and in exploring the CTLA4 gene in a sample of the North African population. The dataset of the current study is composed of 81 patients with AS and 123 healthy controls. All samples were genotyped by TaqMan® allelic discrimination assay. The genetic risk of the HLA-B27 specificity and the CTLA4/CT60 polymorphism were assessed by odds ratios (OR) with 95% confidence intervals (CI). High spondylitis risk was detected for HLA-B27 allele (OR= 14.62, p=10-6 ) in addition to a significant association of the CT60*G allele (OR= 1.89, p=.002). After gender and age stratifications, the association of the CT60*G allele was still significant in females sample (OR= 2.10, p=.001) and when age up to 30years (OR = 2.21, p=.008). Interestingly, the CT60*G allele revealed an increased spondylitis risk in the B27 negative group (OR= 2.81, p=.006). The present work showed in West Algerian population that the HLA-B27 antigen and the variation in the CTLA4 3'UTR region played an important role in the ankylosing spondylitis susceptibility. The heterogeneity of this disease is deduced by genetic difference found between B27+ and B27- groups.

ERAP1/ERAP2 and RUNX3 polymorphisms are not associated with ankylosing spondylitis susceptibility in Chinese Han.

SummaryPrevious studies show that endoplasmic reticulum‐associated aminopeptidase (ERAP1/ERAP2) and runt‐related transcription factor 3 (RUNX3) gene polymorphisms are associated with AS (ankylosing spondylitis) in European Caucasians. However, contradictory results were reported in different Asian populations. The purpose of this study was to determine whether eleven candidate single nucleotide polymorphisms (SNPs) in ERAP1/ERAP2 and six in RUNX3 genes confer susceptibility to AS with or without acute anterior uveitis (AAU) [AS+AAU+ or AS+AAU–] in Chinese Han. Therefore, a case–control association study was performed in 882 AS+AAU–, 884 AS+AAU+ and 1727 healthy controls. Genotyping was performed using the iPLEXGold genotyping assay. A meta‐analysis was performed to assess the association of polymorphisms of ERAP1 with AS susceptibility in Asian populations. No association was found between SNPs of ERAP1/ERAP2/RUNX3 and susceptibility of AS with or without AAU. A case–control study between patients with human leucocyte antigen HLA‐B27‐positive and healthy controls also failed to demonstrate an association of the tested SNP with AS with or without AAU. Moreover, a meta‐analysis showed that there was no association of rs30187, rs27037, rs27980, rs27434 and rs27582 in ERAP1 with AS in Chinese Han. Taken together, 17 SNPs in ERAP1/ERAP2 and RUNX3 genes did not confer disease susceptibility to AS in Chinese Han.

Correlation of PON1 polymorphisms with ankylosing spondylitis susceptibility: A case-control study in Chinese Han population.

Paraoxonase 1 (PON1) modulates the oxidative stress and inflammatory response, thus, it might relate to the risk of ankylosing spondylitis (AS). The aim of present study was to discover the correlation of PON1 polymorphisms (rs662 and rs854560) with PON1 activity and AS risk.Around 128 AS patients and 146 healthy controls were recruited in this case–control study. PON1 polymorphisms were genotyped by direct sequencing. Serum PON1 activity was detected and compared by nonparametric test in different genotypes of PON1 polymorphisms. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to present the relative risk for AS.GG genotype and G allele of rs662 polymorphism were closely correlated with enhanced AS risk (P = .034, OR = 2.318, 95%CI = 1.051–5.113; P = .032, OR = 1.485, 95%CI = 1.033–2.135). PON1 activity was obviously higher in controls than that in AS patients. Significant difference of PON1 activity has been discovered in the different rs662 genotypes (P < .01). rs662 GG genotype carriers had the lowest PON1 activity, followed by AG carriers and the AA carriers. Besides, no significant relationship existed between rs854560 genotypes and AS risk.PON1 rs662 polymorphism is significantly correlated with increased AS risk via inhibiting PON1 activity.

46-Year-Old Man With Lower Back Pain

46-Year-Old Man With Lower Back Pain

Association between the autophagy-related gene ULK1 and ankylosing spondylitis susceptibility in the Chinese Han population: a case–control study

PurposeAnkylosing spondylitis (AS), inflammatory bowel disease and Crohn’s disease (CD) often coexist in the same patient and these diseases have remarkably strong overlaps in genetic association. The association between Unc51like...

The genetic association between polymorphisms in lymphotoxin-α gene and ankylosing spondylitis susceptibility in Chinese group: A case-control study.

The study was designed to reveal the genetic relationship of lymphotoxin-α (LTA) polymorphisms with risk of ankylosing spondylitis (AS) in Chinese Han population.LTA polymorphisms were genotyped by polymerase chain reaction-direct sequencing (PCR-DS) in 138 AS patients and 141 healthy controls. The genotype distribution in control group was checked the status of Hardy–Weinberg equilibrium (HWE). Odds ratio (OR) with 95% confidence interval (95%CI) calculated by χ2 test was used to show effects of LTA polymorphisms on AS risk. Logistic regressive analysis was used to calculate the adjusted OR values. Additionally, the linkage disequilibrium of LTA polymorphisms was examined by Haploview.G allele of rs909253 was significantly higher frequency in AS patients (P = .02), which was associated with the increased risk of AS (OR = 1.53, 95%CI = 1.07–2.18). The carriages of GG genotype in rs909253 showed a high risk of AS occurrence, compared with AA genotype carriers (OR = 2.46, 95%CI = 1.13–5.35). Multivariate analysis demonstrated that the G allele (OR = 1.52, 95%CI = 1.05–2.15) and GG genotype (OR = 2.36, 95%CI = 1.06–5.24) of rs909253 were still positively associated with AS susceptibility. However, there was no significant association between AS risk and rs2239704 or rs2229094.LTA rs909253 polymorphism contributes to the occurrence of AS.