Guo Xia

Male Sexual Dysfunction and Ankylosing Spondylitis: A Systematic Review and Metaanalysis

Objective. No consensus has been reached on sexual dysfunction in men with ankylosing spondylitis (AS). Our study aimed to derive a more precise estimation of the sexual function and its clinical correlations in men with AS. Methods. A metaanalysis was performed and the related literature were searched in PubMed, Elsevier Science Direct, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and in reference lists of articles and systematic reviews. Score of the International Index of Erectile Function (IIEF) was used as the outcome measurement, and standardized mean differences (SMD) with 95% CI were calculated. Results. Eleven studies were included, including 535 men with AS and 430 male controls. Each domain of the IIEF score (erectile function: SMD −0.52, 95% CI −0.68 – −0.37; orgasmic function: −0.72, −1.03 – −0.42; sexual drive: −0.40, −0.62 – −0.18; intercourse satisfaction: −0.86, −1.15 – −0.56; and overall satisfaction: −0.61, −0.91 – −0.32) were lower in men with AS than in controls. In the subgroup analysis, the results did not change except for the sexual drive in the Asians group (−0.15, −0.42–0.13). At metaregression, no study characteristics were significantly associated with effect size of the IIEF score. Conclusion. Sexual function is impaired in male patients with AS and further studies are necessary to better understand risk factors for sexual dysfunction in this population.

Association of IL-1F7 gene with susceptibility to human leukocyte antigen-B27 positive Ankylosing spondylitis in Han Chinese population

Ankylosing spondylitis (AS) is one of the most common inflammatory arthritis, with an estimated prevalence of 0.1%–0.9%. Genetic factors have been strongly implicated in its etiology. Assessed by twin studies, the heritability of AS has been estimated to be 90% [1]. The disease has a strong genetic association with human leukocyte antigen-B27, however, only 1%–5% among those HLA-B27 positive populations developed AS, although most AS patients are HLA-B27 positive. Apparently, HLA-B27 alone does not account for the pattern of AS recurrence. Indeed, the contribution of HLA-B27 to the overall genetic predisposition has been estimated to be only 20%–30%. It has been proposed that non-major histocompatibility complex (non-MHC) genes contribute a major portion of genetic susceptibility to AS [2]. Genome-wide scans have demonstrated several areas of suggestive or significant linkage in non-MHC regions, including 1p, 1q, 2p, 3p, 2q, 5q, 9q, 10q, 11p, 11q, 16q, 17p, 17q and 19q [1,3,4]. Yet, candidate gene studies for non-MHC are limited. A genome-wide scan has identified that a region including interleukin-1 (IL-1) family gene cluster, which lies 123–126 cM from the p-telomere of chromosome 2, is linked to AS susceptibility [4]. Within a 360-kb region, IL-1 gene cluster includes IL-1α (IL1A), IL-1β (IL1B), IL-1F7, IL-1F9, IL-1F6, IL-1F8, IL-1F5, IL-1F10 and IL-1RN genes. This linkage finding was later confirmed by family-based association studies in western Canadian families population [5,6]. Based on these findings, Timms et al. concluded that the IL-1 gene cluster contains a susceptibility locus for AS [7]. Currently studies largely focus on IL-1A/B and IL-1RN genes [8,9]. It is noted that, across different populations, the association between AS and the polymorphisms of IL-1 gene is not identical, although similar [10,11]. Also, information regarding the association between IL-1 polymorphisms and AS is very limited in Chinese population. Therefore, we performed a case–control study on the association between AS and IL-1F7 gene single-marker polymorphism in concert with HLAB27 in Chinese population. We studied 181 unrelated AS patients (111 males and 70 females) with mean age of 26.3 y (SD=6.4 y), and 158 controls individuals (102 males and 56 females) with mean age of 28.2 y (SD=7.4 y). All the cases and controls are HLA-B27 positive. To reduce the influence of population stratification farthest, all the samples in our study are from local Anhuilanders, whose parents are also Anhuilanders. Permission was obtained from all individuals who were enrolled in this study. All patients were recruited from Department of Rheumatology, First Affiliated hospital, Anhui Medical University. All those control individuals had been screened by experienced rheumatism doctors before their blood samples were collected. Clinical diagnosis was carried out strictly according to the modified New York criteria [14]. Two IL-1F7 SNPs were selected from NCBI dbSNP (dbSNP home page).

Association between KIR polymorphisms and ankylosing spondylitis in populations: a meta-analysis.

Abstract Objectives. Published association studies of killer cell immunoglobulin-like receptors (KIRs) and ankylosing spondylitis (AS) in populations are inconsistent. The aim of this study is to determine whether the KIR polymorphisms confer susceptibility to AS in populations by conducting a meta-analysis. Methods. A computer search was carried out up to August 2013 for literature pertaining to AS and KIR polymorphisms. Publications addressing the association between the KIR polymorphisms and susceptibility to AS in populations were selected from the Pubmed, Elsevier Science Direct, China National Knowledge Infrastructure (CNKI) and Chinese Biomedical Literature Database (CBM) databases. The odds ratio (OR) with 95% confidence interval (95%CI) was calculated. Results. A total of 13 case-control studies in 9 articles were included in this meta-analysis. Meta-analysis results identified two positive associations of 2DS4 and 3DS1 with susceptibility to AS in populations. In subgroup analysis, there was a positive association between 2DS4 and susceptibility to AS in Asians, but not in Caucasians. And there were associations between 3DL1, 3DS1 and susceptibility to AS in Caucasians, but not in Asians. Results of subgroup analysis also showed that there were associations between 2DL5, 2DS4, 2DS5, 3DL1, 3DS1 and susceptibility to AS in HLA-B*27-positive patients and HLA-B*27-positive healthy controls. Conclusions. This meta-analysis confirms that 2DS4 and 3DS1 might be potential risk factors for AS in populations.

Increased frequency of circulating follicular helper T cells in patients with ankylosing spondylitis

Abstract Objective. The relationship between circulating follicular helper T (Tfh) cells and ankylosing spondylitis (AS) remains unclear. The aims of our study were to measure the levels of circulating Tfh cells and several related parameters in patients with AS, and examine the correlation of these factors with disease activity. Methods. We designated CD4 + CXCR5 + ICOS+ T cells as circulating Tfh cells. The percentage of circulating Tfh cells was detected using flow cytometry. Plasma IL-21 and immunoglobulin (IgA, IgM, and IgG) levels were quantified using enzyme-linked immunosorbent assay in 60 AS patients and 60 healthy controls (HC). Results. The percentage of circulating Tfh cells was increased in AS patients compared with that in HC. As AS patients were divided into active and inactive groups, the percentage of circulating Tfh cells was significantly increased in active group compared with both inactive group and HC. Plasma IL-21 and immunoglobulin levels were elevated in AS patients, and the differences were significant except IgG. In addition, the percentage of circulating Tfh cells was positively correlated with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and plasma IL-21 levels were positively correlated with plasma immunoglobulin levels. But neither circulating Tfh cells nor BASDAI was significantly correlated with plasma IL-21 and immunoglobulin levels in AS patients, with the exception of significant correlation between BASDAI and plasma IgM levels in active AS patients. Conclusion. Our study has shown the increased percentage of circulating Tfh cells correlated with disease activity, and the high plasma IL-21 levels were associated with high plasma immunoglobulin levels in patients with AS, indicating that the circulating Tfh cells may be associated with the development of AS.

Vitamin D in ankylosing spondylitis: review and meta-analysis.

BACKGROUND The role of vitamin D in ankylosing spondylitis (AS) is largely unknown. This paper aims to examine the association between serum vitamin D levels and susceptibility and disease activity of AS. METHODS We searched the relevant literatures in PubMed, Elsevier Science Direct, Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure (CNKI) and Wanfang (Chinese) Database published before June 2014. Eight independent case-control studies with a total of 533 AS patients and 478 matching controls were selected into this meta-analysis. Standard mean differences (SMDs) with 95% confidence intervals (CIs) were used to assess the levels of serum vitamin D, parathyroid hormone (PTH), serum calcium and alkaline phosphatase (ALP) in cases and controls, respectively. Correlation coefficients (CORs) have been performed to value the correlationship between vitamin D and disease activity (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) of AS patients. RESULTS Meta-analysis results suggested that vitamin D may play a protective role in AS (for total vitamin D: SMD=-0.71, P<0.001; for 25OHD: SMD=-0.66, P=0.002; for 1,25OHD: SMD=-0.72, P=0.19). Differences in PTH and serum calcium levels were not significant in AS (SMD=-0.10, P=0.67; SMD=0.12, P=0.17 respectively), while ALP was associated with AS susceptibility (SMD=0.20, P=0.04). The relationship between serum vitamin D levels and disease activity was statistically significant except for 25OHD versus (vs.) CRP or BASDAI (for CRP vs. 25OHD: COR=-0.22, P=0.08; for BASDAI vs. 25OHD: COR=-0.20, P=0.06, respectively). CONCLUSION The higher levels of serum vitamin D were associated with a decreased risk of AS, and showed an inverse relationship with AS activity.

Single nucleotide polymorphisms of the interleukin-33 (IL-33) gene are associated with ankylosing spondylitis in Chinese individuals: a case–control pilot study

Objectives: Previous studies have found that serum levels of interleukin (IL)-33 are elevated in patients with ankylosing spondylitis (AS). The aim of this study was to determine whether the single nucleotide polymorphisms (SNPs) in the IL-33 gene are associated with susceptibility to AS in a Chinese population. Method: Eight SNPs in the IL-33 gene (rs1891385, rs16924144, rs2210463, rs16924159, rs10118795, rs1929992, rs10975519, and rs1048274) were genotyped by the improved multiplex ligase detection reaction (iMLDR) method in 400 patients with AS and 395 geographically and ethnically matched healthy controls. Haplotypes were constructed after linkage disequilibrium (LD) analysis. Results: There were statistically significant differences at SNPs rs1891385, rs2210463, rs10118795, rs1929992, rs10975519, and rs1048274 in the IL-33 gene between cases and controls. The A allele frequency of rs1891385 was lower in the patient group than in the controls [odds ratio (OR) 0.762] whereas the A allele frequency of rs2210463 and the C allele frequency of rs10118795 and rs1929992 were higher in the patient group than in the controls (OR 1.265, 1.305, and 1.248, respectively). However, there were no differences in the genotype distribution and allele frequencies of rs16924144 and rs16924159 between the patients and controls (p > 0.05). Four SNPs (rs10118795, rs1929992, rs10975519, and rs1048274) were in strong LD and were included in four haplotypes: ht1 (CCCG), ht2 (CCTA), ht3 (CTCG), and ht4 (TTCG). Haplotype ht4 was associated with a decreased risk of AS [OR 0.766, 95% confidence interval (CI) 0.626–0.937, χ2 = 6.761, p = 0.009]. Conclusions: The results suggest that SNPs and the TTCG haplotype of the IL-33 gene are associated with the development of AS in a Chinese Han population.

A single-nucleotide polymorphism marker within the FCRL5 gene and HLA-B27 positive Han Chinese ankylosing spondylitis patients.

The aim of this study was to determine whether FCRL5 genes in concert with human leukocyte antigen-B27 (HLA-B27) genotypes are associated with susceptibility to ankylosing spondylitis (AS) in Chinese population. One hundred and sixty-nine HLA-B27-positive AS patients (107 males and 62 females) and 184 HLA-B27-positive matched controls (112 males and 72 females) were analyzed from Han Chinese populations by case-control design, and their samples were genotyped using a panel of two single-nucleotide polymorphism (SNP) markers (rs6427384, rs12036228) within the FCRL5 gene by ligase detection reactions (LDRs) and the HLA-B27 subtypes were determined by polymerase chain reaction (PCR) using sequence-specific primer (SSP) methods. Our results show that in addition to B27, the SNPs rs6427384 and rs12036228 were associated with AS, and the C-T haplotype was higher in cases with AS than in the control population [74.8% vs 63.6%, Fishers P = 0.003, odds ratio (OR) = 1.660,95% confidence interval (CI) = 1.184-- 2.326]. Our results suggest that, in addition to HLA-B27, a novel polymorphism within the FCRL5 gene confers susceptibility to AS in Han Chinese population.

Associations between ERAP1 polymorphisms and ankylosing spondylitis susceptibility: An updated meta-analysis

Abstract Objective. The relationship between the endoplasmic reticulum aminopeptidase 1 (ERAP1) polymorphisms and ankylosing spondylitis (AS) was inconsistent in the recent literatures, a meta-analysis was therefore performed. Methods. A total of 25 independent studies with 24,271 AS patients and 42,666 controls were included after searching electronic databases for studies published before June 2014. The pooled and individual odds ratios (ORs) with 95% confidence intervals (CIs) were presented to assess the associations between ERAP1 polymorphisms and AS in different ethnicities. Results. This meta-analysis includes 25 studies that investigate 8 single nucleotide polymorphisms (SNPs; rs17482078, rs30187, rs2287987, rs27044, rs26653, rs10050860, rs27037, and rs27434) in ERAP1 gene. Overall, six SNPs were associated with AS; two SNPs (rs27044 and rs26653) were not when all studies were pooled into the meta-analysis (rs27044 G vs. C, OR = 1.058, 95% CI = 0.827–1.354; rs26653 C vs. G, OR = 1.154, 95% CI = 0.937–1.422). In Caucasians, all the 8 SNPs were significantly associated with AS. But 5 SNPs (rs17482078, rs2287987, rs27044, rs26653, and rs10050860) did not show statistical association with the risk of AS in Asians. Conclusion. ERAP1 polymorphisms were associated with AS in Caucasians, but their association with AS in Asians needs further exploration.

Lack of Association Between TESPA1 Gene Polymorphisms (rs1801876, rs2171497, rs4758994, and rs997173) and Ankylosing Spondylitis in a Chinese Population

We investigated whether TESPA1 gene polymorphisms were associated with increased risk of developing ankylosing spondylitis (AS). We also studied whether TESPA1 gene interacts with environmental factors. A total of 494 patients with AS and 478 matched healthy controls were genotyped for four SNPs (rs1801876, rs2171497, rs4758994, and rs997173) in the TESPA1 gene. We found no evidence of association between these SNPs and AS susceptibility, and between their haplotypes and the disease. But, patients with rs1801876 GA, GG, and AA genotypes had significantly different Bath Ankylosing Spondylitis Functional Index (BASFI) scores (p = 0.023). There were significantly different visual analogue scale (VAS) night pain assessment scores (p = 0.040) and BASFI scores (p = 0.023) among different genotypes at rs2171497 locus. There were also significantly different chest expansion scores (p = 0.042) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores (p = 0.014) among different genotypes at rs997173 locus. For multiple testing, Bonferroni correction was performed. After Bonferroni correction, clinical characteristics of these three loci showed association between different genotype groups. These findings indicated that the TESPA1 gene is not involved in AS genetic predisposition in the Han Chinese population; however, it may play an important role in the clinical characteristics of AS.