It has been reported that two single nucleotide polymorphisms (SNP) Taq1A and -141C Ins/Del in the DRD2 gene may be associated with susceptibility to schizophrenia. Due to inconclusive and mixed results, a meta-analysis was conducted to further clarify the relationship between the two SNP and schizophrenia susceptibility. A systematic literature search for the association of these two SNP with schizophrenia susceptibility was conducted using PubMed, ScienceDirect, Chinese Biomedical Literature Database, and Chinese National Knowledge Infrastructure. Odds ratios (OR) with 95% confidence intervals (CI) were used to assess the strength of the associations reported. A total of 5558 schizophrenic patients and 6792 healthy controls from 31 articles were included in this study. Evidence regarding the association between -141C Ins/Del polymorphism and schizophrenia was found in the allele frequency comparison (Ins versus Del: OR 1.29, 95% CI 1.06-1.57; p=0.01, Praw=0.1, PFalse Discovery Rate=0.023). In ethnic subgroup analysis, the result revealed that the 141C Ins/Del polymorphism was associated with schizophrenia in all genetic models in Asians, but not in Caucasians. For Taq1A polymorphism, a significant association was found in the allele frequency (A1 versus A2: OR 0.71, 95% CI 0.52-0.98, p=0.03). Stratification by ethnicity indicated an association between the Taq1A polymorphism and schizophrenia in Asians, but not Caucasians. The present study suggests that the -141C Ins/Del polymorphism carries a significantly increased risk of schizophrenia, while the Taq1A polymorphism carries a significantly decreased risk of schizophrenia susceptibility in Asians.

Objectives. To explore the association of β-defensin gene copy number variations (CNVs) with ankylosing spondylitis (AS). Methods. In this study, 405 unrelated Chinese Han patients with AS and 401 unrelated healthy controls were enrolled. The copy numbers of DEFB4 gene (2 fragments) were measured by AccuCopy™ methods. The association of DEFB4 gene CNVs with AS susceptibility was analyzed by chi-square and logistic regression models. Besides, P values, odds ratio, and 95% confidence intervals (CIs) were used to estimate the effects of risk. Results. The range of DEFB4_1 CN was 0–7 and the range of DEFB4_2 CN was 1–8 both in patients and controls. P values of χ2 trend test for the association of DEFB4_1 and DEFB4_2 with AS were 0.607 and 0.005, respectively. The results of DEFB4_2, compared with the individual having median 3 copies, those carrying ≤ 2-copies [OR = 0.68, 95%CI: (0.46, 0.99), P = 0.049; adjusted OR = 0.69, 95%CI(0.47, 1.03), P = 0.067.]; and those carrying ≥ 4-copies [OR = 0.62, 95%CI: (0.45, 0.86), P = 0.004; adjusted OR = 0.64, 95%CI: (0.46, 0.88), P = 0.006], were significantly associated with decreasing risk of AS. Univariate analysis showed that both DEFB4_1 and DEFB4_2 were associated with Bath AS Disease Activity Index or BASDAI. After adjusted by age, sex, and disease duration, the results changed little, which demonstrated that high copies may be linked with decrease in the risk of disease severity [OR = 0.71, 95%CI: (0.56, 0.90), P = 0.005; OR = 0.75, 95%CI: (0.60, 0.94), P = 0.013, respectively]. Conclusions. The CNs of DEFB4 gene may be associated with AS and involved in disease progression.

Many publications with conflicting results have evaluated serum levels of copper (Cu) and zinc (Zn) in patients with rheumatoid arthritis (RA). To derive a more precise estimation of the relationship, a meta-analysis was conducted. Relevant published data were retrieved through PubMed, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Database (CBM) before September 20, 2014. Weighted mean difference (WMD) with a 95 % confidence interval (95 % CI) was calculated using STATA 11.0. A total of 26 studies, including 1444 RA cases and 1241 healthy controls, were collected in this meta-analysis. Pooled analysis found that patients with RA had a higher serum level of Cu and a lower serum Zn level than the healthy controls (Cu (μg/dl), WMD = 31.824, 95 % CI = 20.334, 43.314; Zn (μg/dl), WMD = −12.683, 95 % CI = −19.783, −5.584). Subgroup analysis showed that ethnicity had influence on the serum level of Cu (μg/dl) (Caucasian, WMD = 43.907, 95 % CI = 35.090, 52.723, P < 0.001; Asian, WMD = 14.545, 95 % CI = −12.365, 41.455, P = 0.289) and Zn (μg/dl) (Caucasian, WMD = −11.038, 95 % CI = −23.420, 1.344, P = 0.081; Asian, WMD = −14.179, 95 % CI = −18.963, −9.394, P < 0.001) in RA and healthy controls. No evidence of publication bias was observed. This meta-analysis suggests that increased serum level of Cu and decreased serum level of Zn are generally present in RA patients.

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.

In this brief communication, we investigate the role of DEFB103 gene copy number variation (CNV) in ankylosing spondylitis (AS) susceptibility. A total of 807 Chinese individuals including 406 AS patients and 401 controls were enrolled. The DEFB103 copy number was measured by two sets of probes to obtain a stable result in a custom-by-design Multiplex AccuCopy(™) kit (Genesky Biotechnologies Inc., Shanghai, China) based on a multiplex fluorescence competitive polymerase chain reaction (PCR) principle. The copy number of DEFB103 ranged from 2 to 6 in both AS patients and controls. Mann-Whitney U test and chi-squared test were performed to analyze the difference of DEFB103 copy number between AS patients and controls while no statistical difference has been found. We considered the copy number of DEFB103 gene may not associate with susceptibility to AS.

Objective This study aims to determine whether the genetic polymorphisms of IL-12B gene is a susceptibility factor to Ankylosing spondylitis (AS) in mainland Han Chinese population. Method Eight single-nucleotide polymorphisms (SNPs) (rs10045431, rs11167764, rs3212227, rs6556412, rs6556416, rs6871626, rs6887695 and rs7709212) in the IL-12B gene were genotyped by iMLDR Assay technology in 400 patients [96% (384/400) HLA-B27(+)] and 395 geographically and ethnically matched healthy controls in mainland Han Chinese population. The correlation between IL-12B genetic polymorphisms and AS activity index (BASDAI, BASFI) were tested. Results The significant difference was found in genotype distribution between AS and healthy controls (χ2 = 6.942, P-value = 0.031) of the SNP rs6871626. Furthermore, significant evidence was also detected under the recessive model for minor allele A. The AA genotype carrier had 1.830 fold risk compared with C allele carrier (with CC and AC genotypes) [OR (95% CI) = 1.830 (1.131-2.961), P-value = 0.014]. Nevertheless, the difference was no longer significant after Bonferroni correction. Subset analysis on cases with HLA-B27(+) did find the same results. Three genotypic groups (AA, CC and CA) in rs6871626 site was highly associated with the BASDAI and BASFI (P-value = 0.012 and P-value = 0.023, respectively), after adjustment for effect of age, sex, and disease duration, the P-value was 0.031 and 0.041, respectively. The AA genotype of rs6871626 was also significantly correlated with an increased BASDAI and BASFI compared to the AC and CC genotypes in AS patients. Conclusion Our findings suggest that rs6871626 may be associated AS susceptibility and with disease activity (BASDAI, BASFI) in mainland Han Chinese population.

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.

Objectives: The results of studies on association between KIR (killer cell immunoglobulin-like receptors) polymorphisms and susceptibility to RA (rheumatoid arthritis) are inconsistent. To comprehensively evaluate the effect of KIR polymorphisms on the risk of RA, a meta-analysis was carried out.Methods: The Web of Science, PubMed, the Chinese Biomedical Database (CBM) and Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched to select studies on the association between KIR polymorphisms and RA. The odds ratio (OR) with 95% confidence interval (95%CI) was obtained.Results: Nine qualified case-control studies were included in this meta-analysis. The results showed there were two positive associations of 2DL1, 2DS1 (OR2DL1 = 2.20, 95%CI = 1.20-4.01, P-raw = 0.01, P-FDR = 0.03; OR2DS1 = 1.84, 95%CI = 1.19-2.85, P-raw = 0.006, P-FDR = 0.018) and one negative association of 2DL3 (OR2DL3 = 0.42, 95%CI = 0.22-0.79, P-raw = 0.006, P-FDR = 0.018) with susceptibility to RA in East Asians, but not in Caucasians.Conclusion: The current meta-analysis provides evidence that 2DL3 might be a potential protective factor and 2DLI, 2DS1 might be risk factors for RA in East Asians but not in Caucasians. (C) 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

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.

The aim of this study was to explore the interaction between FCRL4 gene and environmental factors in patients with ankylosing spondylitis. Two hundred ninety-seven ankylosing spondylitis (AS) Han Chinese patients were selected who were diagnosed at the Department of Rheumatology, First Affiliated Hospital, Anhui Medical University, in accordance with the modified New York criteria. The single nucleotide polymorphism (SNP) was genotyped by multiplex SNaPshot technique. The interaction between FCRL4 gene and ten environmental factors in AS patients was assessed by using a case-only study. The interaction between FCRL4 gene (rs2777963) and environmental factors was analyzed by chi-square test and logistic models. p values, odds ratio, and 95 % confidence intervals (CIs) were used for estimating the effects of interaction. Odds ratio (OR) for the interaction of gene × environment (G × E) between drinking group and non-drinking group was 2.61 [95 % CI (1.30, 5.23), p = 0.007], with statistical significance. Within the cooking oil group, there also may be an interaction of G × E between main animal oil and main plant oil [OR = 10.55, 95 % CI (5.55, 20.04), p < 0.001]. However, there was no interaction between FCRL4 gene and the other eight environmental factors in patients with AS. The observed significant gene-environment interaction suggests that drinking and cooking oil with FCRL4 gene has a significant interaction. Drinking and cooking oil may be risk exposure factors to take a combined action with predisposing genes in patients with AS. A larger sample case-control study is needed to illustrate the interaction mechanism in the further study.

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.

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, chi(2) = 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.

Schizophrenia is a common, complex multi-factorial psychiatric disorder. Many studies have reported associations between the C957T and C939T polymorphisms in Dopamine D2 receptor (DRD2) gene and schizophrenia, but results are inconsistent. To derive a more precise estimation of the relationship, a meta-analysis was conducted to systematically summarize the possibility. We included 13 articles involving 3079 schizophrenia cases and 3851 healthy controls. Positive associations were found between C957T polymorphism and schizophrenia risk in C vs. T (OR=1.26, 95% CI=1.09-1.46, Praw=0.002, PFDR=0.005) and CC+CT vs. TT (OR=1.47, 95% CI=1.25-1.73, Praw<0.001, PFDR<0.001). When stratified by race, a significantly increased risk of schizophrenia was observed in Caucasians, but not in Asians. No association between C939T polymorphism and schizophrenia was found in overall or Asian population. Our study suggested that C957T of DRD2 gene polymorphism is likely to be a risk factor for schizophrenia, especially in Caucasian.

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 250HD: SMD = -0.66, P = 0.002; for 1,250HD: 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 250HD versus (vs.) CRP or BASDAI (for CRP vs. 250HD: COR = -0.22, P = 0.08; for BASDAI vs. 250HD: 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. (C) 2014 Elsevier B.V. All rights reserved.

The aim of our meta-analysis was to assess the association between NFKB1 -94ins/delATTG promoter polymorphism and cancer risk. Eleven studies that included data from 2,743 cases and 2,195 controls were identified. When all groups were pooled, we did not detect the association between NFKB1 -94ins/delATTG promoter polymorphism and cancer risk. In the subgroup analysis, we detected the association of NFKB1 -94ins/delATTG promoter polymorphism with cancer in Caucasian population. The association also was found in Asian population. This meta-analysis demonstrates the association of NFKB1 -94ins/delATTG promoter polymorphism with cancer in Caucasian and Asian populations, and this association is ethno-specific.