Meta-analysis of FKBP5 gene polymorphisms association with treatment response in patients with mood disorders

The aim of our study was to assess the association between FKBP5 gene polymorphisms and treatment response in patients with mood disorders using a meta-analysis. Eight separate studies that included data from 2199 subjects were identified. Meta-analysis was performed for three FKBP5 gene polymorphisms (rs1360780, rs3800373, and rs4713916). A significant association of FKBP5 gene rs4713916 polymorphism and response rate was found in patients with mood disorders (Overall: A versus G: OR = 1.28, 95%CI = 1.06–1.53, P = 0.01; GA + AA versus GG: OR = 1.32, 95%CI = 1.05–1.67, P = 0.02. Caucasian: A versus G: OR = 1.28, 95%CI = 1.06–1.55, P = 0.01; GA + AA versus GG: OR = 1.33, 95%CI = 1.04–1.70, P = 0.02). However, we did not detect the association between FKBP5 gene rs1360780 and rs3800373 polymorphisms and treatment response in patients with mood disorders (P > 0.05). This meta-analysis demonstrates that treatment response in patients with mood disorders is associated with FKBP5 gene rs4713916 polymorphism, but not rs1360780 and rs3800373.     

Association of ADIPOQ polymorphisms with obesity risk: A meta-analysis

Background

The association between ADIPOQ polymorphisms and the risk of obesity remains controversial. We perform a comprehensive meta-analysis to clarify the current understanding of this association.

Methods

We searched for relevant studies in PubMed, Embase and Cochrane library before February 2014. The strengths of the association between ADIPOQ polymorphisms and obesity risk were estimated by odds ratios (OR) with 95% confidence intervals (CI).

Results

Eighteen case–control studies analyzing four SNPs (rs17300539, rs266729, rs1501299 and rs2241766) of ADIPOQ gene were eligible for the present meta-analysis. The pooling results showed that rs17300539 (2GG+GA vs. 2AA+GA: OR = 0.78, 95%CI = 0.69–0.89) and rs1501299 (2GG+GA vs. 2AA+GA: OR = 0.89, 95%CI = 0.80–0.98) were associated with obesity risk in Caucasian ethnicity. The rs266729 were associated with obesity risk in Asian ethnicity (2CC+CG vs. 2GG+GCG: OR = 0.77, 95%CI = 0.65–0.92). However, there were no associations between rs2241766 and the obesity risk (P > 0.05). No publication bias was found among these studies (all P > 0.05).

Conclusions

This study suggests that ADIPOQ rs17300539 and rs1501299 are associated with risk of obesity in Caucasian ethnicity, and the rs266729 is associated with obesity risk in Asian ethnicity. However, there is no association between rs2241766 and obesity risk.     

Association of osteopontin polymorphisms with nasopharyngeal carcinoma risk

No previous study has reported the association of osteopontin polymorphisms with nasopharyngeal carcinoma (NPC) risk. We aimed to investigate the association in a Chinese population. Four variants of osteopontin, rs11730582, rs1126772, rs9138, and rs4754 polymorphisms, were assessed in a case-control study which consists of 108 NPC patients and 210 health controls, by using polymerase chain reaction – restriction fragment length polymorphism method. Serum osteopontin levels were measured by enzyme-linked immunosorbent assay. The serum osteopontin levels were significantly higher in NPC patients than those in controls (P < 0.01). Carriers of CC and CT genotype of rs11730582 presented lower serum osteopontin levels than those of TT genotype carriers (P < 0.05). Genotypes CT and CT + CC of rs11730582 were associated with the risk of NPC (CT:OR = 0.57, 95%CI = 0.34–0.94; CC + CT:OR = 0.54, 95%CI = 0.34–0.87). Haplotype analysis revealed that haplotype T-A-A-C of rs11730582, rs1126772, rs9138, and rs4754 was associated with NPC risk (OR = 0.49, 95%CI = 0.27–0.86). Stratification analysis showed that genotypes CT and CT + CC of rs11730582 were associated with tumor stage and lymph node metastasis (P < 0.05). No associations were found between rs1126772, rs9138, and rs4754 polymorphisms and NPC risk (P > 0.05). The variant rs11730582 of osteopontin is associated with NPC risk. It potentially serves as a genetic marker of NPC predisposition.     

Meta-analysis of the relationship between 14bp insertion/deletion polymorphism of HLA-G gene and susceptibility to systemic lupus erythematosus

We performed a meta-analysis to examine the relationship between the human leukocyte antigen-G (HLA-G) 14 base pairs sequence (14bp) insertion (ins)/deletion (del) polymorphism to systemic lupus erythematosus (SLE). Eligible studies were extracted in PubMed, Embase, Cochrane Library and CNKI (Chinese) up to March 31, 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated to evaluate the strength of the association. Finally, 7 studies with 1864 cases and 2259 controls were involved in this meta-analysis. Overall, the HLA-G 14bp ins/del polymorphism was significantly associated with SLE susceptibility (ins vs. del: OR = 1.179, 95%CI = 1.037–1.341, P = 0.012; ins/ins vs. del/del: OR = 1.394, 95%CI = 1.153–1.684, P = 0.001; ins/del vs. del/del: OR = 1.199, 95%CI = 1.041–1.382, P = 0.012; ins/ins + ins/del vs. del/del: OR = 1.252, 95%CI = 1.097–1.430, P = 0.001). When stratified by ethnicity, significance was found in Asians (ins/ins vs. del/del: OR = 1.326, 95%CI = 1.001–1.756, P = 0.049) and Caucasians (ins/ins vs. del/del: OR = 1.454, 95%CI = 1.126–1.878, P = 0.004; ins/del vs. del/del: OR = 1.288, 95%CI = 1.051–1.579, P = 0.015; ins/ins + ins/del vs. del/del: OR = 1.340, 95%CI = 1.106–1.623, P = 0.003). Our results suggest that the HLA-G 14bp insertion allele might act as an increased risk against SLE. Besides, this is the first meta-analysis to report an association between the HLA-G 14bp ins/del polymorphism and SLE. Larger and well-designed studies are needed to further confirm these findings.     

Association between promoter polymorphisms of the nicastrin gene and sporadic Alzheimer's disease in North Chinese Han population

Increasing evidences have shown that nicastrin (NCSTN) plays a crucial role in γ-cleavage of the amyloid precursor protein (APP). Inhibition of NCSTN demonstrated an altered γ-cleavage activity, suggesting its potential implication in developing Alzheimer's disease (AD). We detected the NCSTN gene promoter region in 359 sporadic AD (SAD) patients and 331 controls and found three promoter single nucleotide polymorphisms (SNPs): −1216C/A (rs2147471), −796T/G (rs10752637) and −436C/T (rs1324738). For −1216C/A, there were significant differences in the allele and genotype frequency between AD and control subjects (allele P = 0.031, genotype P = 0.017). The allele and genotype frequencies remained significant before and after APOE?4 stratification. The −1216CC carriers increased 2-fold risk for the development of SAD compared to the carriers with −1216CA and AA genotypes (OR = 2.049, 95%CI = 1.410–2.976, P = 0.000). For −796T/G, there were significant differences in the genotype frequency between SAD and control subjects (P = 0.009). This trend is still obvious in the subjects without APOE?4 allele. The −796GG carriers might decrease the risk compared to the carriers with −796TG and TT genotypes (OR = 0.602, 95%CI = 0.393–0.932, P = 0.022). No significant difference was detected either in genotype or in allele frequencies between SAD and control for −436C/T, even after APOE?4 stratification. The haplotype −1216A/−796G may be a protective factor for SAD (OR = 0.795, 95%CI = 0.636–0.995, P = 0.045). Our investigation suggests that −1216C/A and −796T/G are probably related to the development of SAD.     

Toll-like receptor 6 gene polymorphisms increase the risk of bovine tuberculosis in Chinese Holstein cattle

Our present study aimed to investigate the effect of four SNPs (G1793A, C1859A, A1980G, G1934A) in toll-like receptor 6 (TLR6) on bovine tuberculosis (bTB) resistance in a case–control study. A total of 603 Chinese Holstein cattle (264 from a dairy farm of Henan province, 339 from Hubei province) were selected to analyze the genotype of TLR6 gene by PCR-RFLP. Genotype frequencies of C1859A and A1980G site differed significantly between bTB-infected and non-infected cows (χ² = 6.062, P = 0.048 and χ² = 6.749, P = 0.034, respectively). Relative risk of tuberculosis incidence result showed that genotypes of AA or CA had greater relative risk (OR = 2.730, 95%CI = 0.869–8.573; OR = 1.547, 95CI% = 0.803–2.982, respectively) than those with genotype CC at C1859A site between bTB-infected and non-infected animals. Genotypes of GG or GA had greater relative risk (OR = 2.986, 95%CI = 1.245–7.165; OR = 1.582, 95%CI = 0.734–3.409, respectively) than those with genotype AA at A1980G site. No significant association can be inferred from G1793A and G1934A polymorphism site. The present study suggests that variants in the TLR6 gene are associated with susceptibility to bTB and the TLR6 gene may be considered as a candidate gene for bTB resistance.     

The interleukin-6 gene −572C/G promoter polymorphism modifies Alzheimer's risk in APOE ɛ4 carriers

Inflammatory response is involved in the etiopathology of Alzheimer's disease (AD). Interleukin-6 (IL-6), a pleiotropic inflammatory cytokine, was reported to be associated with both increased Aβ aggregation and the appearance of hyperphosphorylated tau in AD brain. To explore the association of genetic variants in the promoter of IL-6 gene with sporadic AD (SAD), a case–control study was conducted in a North Chinese Han population. A systematic screening of IL-6 promoter was performed using direct sequencing and two polymorphisms were obtained including −572C/G (rs1800796) and −384A/T (rs7802308). Definitive genotyping of these markers and apolipoprotein E (APOE) polymorphism were surveyed in 341 SAD patients and 421 controls. The results revealed no significant differences in the distributions of alleles or genotypes between SAD and control groups. However, there was an interaction between −572C/G and APOE genotypes (P = 0.016) using logistic analysis. In the subjects with APOE ?4, there were significant differences in the allele (P = 0.004) and genotype (P = 0.004) distributions of −572C/G polymorphism between SAD and control groups. The −572CC genotype increased risk for AD by 3.301-fold (Wald = 11.093, adjust OR = 3.301, 95% CI = 1.635–6.665, P = 0.001) compared to CG + GG genotype. The present results suggest the −572 polymorphism could modify the risk for SAD in APOE ?4 carriers.     

Association of two polymorphisms rs2910164 in miRNA-146a and rs3746444 in miRNA-499 with rheumatoid arthritis: A meta-analysis

Background

It has been reported that two single nucleotide polymorphisms (SNPs) rs2910164 in miRNA-146a and rs3746444 in miRNA-499 might be associated with the susceptibility to rheumatoid arthritis (RA). Owing to mixed and inconclusive results, we conducted a meta-analysis to systematically summarize and clarify the association between the two SNPs and RA risk.

Methodology/main results

A systematic search of studies on the association of two SNPs with susceptibility to RA was conducted in PubMed and Embase. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size. A total of 6 case-control studies on rs2910164 and 3 studies on rs3746444 were included. Though no evidence of association was found between rs2910164 polymorphism and RA risk in all the genetic models, a trend of reduced risk could be drawn. (C versus G: OR = 0.93, 95% CI 0.82–1.05; GC versus GG: OR = 0.89, 95% CI 0.73–1.10; CC versus GG: OR = 0.84, 95% CI 0.64–1.10; GC/CC versus GG: OR = 0.89, 95% CI 0.73–1.08; CC versus GC/GG: OR = 0.94, 95% CI 0.77–1.14). A significant increased risk of RA was observed in the rs3746444 polymorphism in homozygote comparison, recessive comparison, and allele comparison, but there was insufficient data to fully confirm the association of RA and rs3746444 in miRNA-499.

Conclusions

MiRNA-146a rs2910164 polymorphism is not associated with RA risk, while miRNA-499 rs3746444 polymorphism is correlated with RA risk. However, the results of miRNA-499 rs3746444 should be interpreted with caution due to limited sample and heterogeneity. Large-scale and well-designed studies are needed to validate our findings.     

Investigation of gene–gene interactions between CD40 and CD40L in Polish multiple sclerosis patients

CD40–CD40L interaction is necessary for the activation of both humoral and cellular immune response and has been suggested to play a role in the pathogenesis of multiple sclerosis (MS). Therefore, we analyzed the combined influence of the CD40 and CD40L variants on MS susceptibility and progression on well-defined Polish population. Our investigation revealed that CT individuals in rs1883832 locus of CD40 possessed almost 1.5-fold higher risk for MS than CC individuals (OR = 1.44; 95%CI = 1.03–2.1; p = 0.032), while this risk for TT individuals was almost 2.5-fold higher (OR = 2.36; 95%CI = 1.19–4.78; p = 0.014).     

Association between interleukin-1β C (3953/4)T polymorphism and chronic periodontitis: Evidence from a meta-analysis

The aim of this study was to perform a meta-analysis to evaluated the association between interleukin-1β (IL-1β) C(3953/4)T polymorphism and chronic periodontitis (CP). Systematic searches of electronic databases and hand searching of references were performed, including PubMed, Embase and Web of Science. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated. Publication bias was tested by Begg’s funnel plot and Egger’s regression test. Sensitivity analysis was conducted by limiting the meta-analysis studies conforming to Hardy–Weinberg equilibrium (HWE) or high quality (score ? 7). Data analyses were carried out by Stata 11.0. There were significant associations between IL-1β C(3953/4)T polymorphism and CP (for T allele vs. C allele: OR = 1.30, 95%CI = 1.05–1.60, p = 0.02; for T/T vs. C/C: OR = 1.66, 95%CI = 1.12–2.45, p = 0.01; for C/T + T/T vs. C/C: OR = 1.28, 95%CI = 0.99–1.65; and for T/T vs. C/T + C/C: OR = 1.62, 95%CI = 1.15–2.29, p = 0.006). When stratified by ethnicity, statistically significantly elevated risk was found for Caucasians, but not for Asians. When stratified by study design, evidences of significant association was observed between IL-1β C(3953/4)T polymorphism and CP in both population-based studies and hospital-based studies. This meta-analysis indicates that there is strong evidence for association between IL-1β C(3953/4)T polymorphism and CP.     

Polymorphisms of interleukin 6 and interleukin 10 in Egyptian people with Behcet's disease

Cytokines play critical roles in the pathogenesis of Behçet's disease (BD). They mediated many of the effectors and regulatory functions of immune and inflammatory responses. Many studies have linked Interleukin-6 (IL-6) and Interleukin-10 (IL-10) pathologically to BD. Thus, this study aimed to investigate the associations between IL-6 and IL-10 promoter single-nucleotide polymorphisms (SNPs) and the susceptibility to BD and their implication on plasma levels. We genotyped IL-6 −174 G/C (rs1800795) using Mutagenically Separated Polymerase Chain Reaction PCR (MS-PCR) and IL-10 −1082 G/A (rs1800896) and −819 C/T (rs1800871) using Sequence Specific Primer PCR (SSP-PCR) in 87 Egyptian patients and 97 controls. The plasma levels of IL-6 and IL-10 were measured using Enzyme-linked Immunosorbent Assay (ELISA). Significant increase in the frequency of −1082 GG genotype (P < 0.05, OR = 2.25, 95%CI = 1.03–4.91) and significant decrease in the frequency of −1082 GA genotype (P < 0.05, OR = 0.53, 95%CI = 0.29–0.96) was demonstrated in BD patients compare to controls. Patients with genital ulcer had significantly lower frequency of −1082 GG (P < 0.05, OR 0.2, 95% CI = 0.04–0.99) and G allele (P < 0.05, OR = 0.28, 95%CI = 0.08–0.93), while patients with ocular manifestations had significantly higher frequency of −1082 G allele (P < 0.01, OR = 2.28, 95%CI = 1.19–4.36). BD patients had significantly higher level of IL-6 (P < 0.001) and significantly lower level of IL-10 (P < 0.001) compared to controls. The changes in the level of cytokines were independent of any genotype of IL-6 or any genotype/haplotype of IL-10. Patients with active disease state had significantly higher level of IL-6 compared to patients in remission (P < 0.05). In conclusion, our preliminary study indicates that the polymorphism at IL-10 −1082 G/A may play a role in BD susceptibility. The significant increase in IL-6 level and the significant decrease in IL-10 level in BD patients were independent of any particular genotype in IL-6 or any particular genotype/haplotype in IL-10.     

Association between somatostatin gene polymorphisms and sporadic Alzheimer's disease in Chinese population

Recent evidence has suggested that down-regulation of somatostatin (SST) expression in the human brain during early stages of aging leads to an elevation in the steady-state levels of Aβ and therefore may be involved in Alzheimer's disease (AD) progression. We hypothesized that alterations in the SST gene might alter its expression or function and also play a role in the pathogenesis of sporadic AD (SAD). First, we sequenced the entire SST gene in 25 randomly selected controls and 25 SAD patients and then screened for C/T polymorphisms (rs4988514) in the 3′ un-translated region. We genotyped rs4988514 polymorphisms as well as apolipoprotein ?4 (APOE ?4) status in 309 SAD patients and 276 normal controls with restriction fragment length polymorphism (RFLP) analysis. Results showed that the C allele of the rs4988514 polymorphism had an increased incidence in the SAD group compared to the control group (p = 0.042). In subjects with the APOE ?4 allele, the presence of both the CC genotype and the C allele of this polymorphism were elevated in the SAD group compared to the control group (genotype p = 0.027, allele p = 0.011). In the whole study group, the age, sex, and APOE ?4 adjusted OR for the risk of AD in C allele carriers was 1.313 (95%CI = 1.068–2.234, p = 0.027) whereas within only APOE ?4 allele carriers, the adjusted OR increased to 2.734 (95%CI = 1.236–5.862, p = 0.012). Our results supported the notion that the C allele of the rs4988514 polymorphism may increase the risk for AD in the Chinese population and possibly have additive effect with the APOE ?4 allele.     

No association between IL-1β −31 C/T polymorphism and the risk of duodenal ulcer: A meta-analysis of 3793 subjects

The aim of this study was to perform a meta-analysis to investigate a more authentic association between IL-1β −31 C/T polymorphism and duodenal ulcer (DU). Systematic searches of electronic databases Embase, PubMed and Web of Science were performed. Study selection, data abstraction and study quality evaluation were independently conducted in duplicate. Statistical analyses were conducted using software Stata 11.0. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were applied. Publication bias was tested by Begg’s funnel plot and Egger’s regression test. A total of 12 studies including 1151 cases and 2642 controls were included in our final meta-analysis. There was no evidence of significant association between IL-1β −31 C/T polymorphism and DU (allelic model: OR = 0.96, 95%CI = 0.86–1.07; additive model: OR = 0.85, 95%CI = 0.67–1.07; dominant model: OR = 0.95, 95%CI = 0.81–1.13; and recessive model: OR = 0.95, 95%CI = 0.79–1.15). Significant association was found in additive model for PB subgroup (OR = 0.65, 95%CI = 0.44–0.96) and recessive model for non-Asian subgroup (OR = 0.72, 95%CI = 0.52–0.99). In conclusion, our meta-analysis suggested that there was no evidence of significant association between IL-1β −31 C/T polymorphism and DU with or without Helicobacter pylori infection in overall population, whereas significant association was found by subgroup analyses which showed protective effect of C/C genotype against DU risk.     

CD226 Gly307Ser association with multiple autoimmune diseases: A meta-analysis

Background

Recently, there has been increasing evidence shown that a non-synonymous exchange (Gly307Ser/rs763361) of the CD226 gene on chromosome 18q22 is linked to several autoimmune diseases (ADs) including type 1 diabetes (T1D), celiac disease (CED), rheumatoid arthritis (RA), multiple sclerosis (MS), Grave’s disease, Wegener’s granulomatosis (WG), psoriasis, and primary sicca syndrome (pSS). Taking into consideration that different autoimmune diseases may share some common pathogenic pathways and in order to assess the overall relationship between CD226 Gly307Ser (rs763361) polymorphism and multiple autoimmune diseases, we performed this meta-analysis.

Method

All eligible case-control studies were searched in the US National Library of Medicine’s PubMed and Embase database. Crude odds ratios (OR) with 95% confidence intervals (CI) were conducted to assess the association.

Results

7876 cases and 8558 controls from 7 published studies which were selected from 149 articles identified by a search of the US National Library of Medicine’s PubMed and Embase databases for the period up to 25th April 2012. The total OR for ADs associated with the T allele was 1.19 (95%CI = 1.12–1.27) by random effects model. Significantly increased risks were also observed in the South American (OR = 1.72, 95%CI = 1.34–2.20), Asian (OR = 1.46, 95%CI = 1.01–2.10), and European (OR = 1.29, 95%CI = 1.07–1.58). Similarly, significant associations were observed in two genetic models (OR = 1.41, 95%CI = 1.23–1.62 in a codominant model; OR = 1.33, 95%CI = 1.18–1.50 in a recessive model).

Conclusion

This meta-analysis provided evidence that CD226 Gly307Ser (rs763361) is significantly associated with the risk of multiple autoimmune diseases.     

Support for the involvement of the ERBB4 gene in schizophrenia: A genetic association analysis

Cellular, animal and human studies support the involvement of aberrant NRG–ErbB signaling in the pathogenesis of schizophrenia. The aim of the present study was to examine whether genetic variation in the human ERBB4 gene is associated with susceptibility to schizophrenia. Two hundred and twenty-seven unrelated chronic inpatients with schizophrenia were enrolled in the study, and the genetic variation in the polymorphisms of the ERBB4 gene in the patients was compared with that of the control group, which consisted of 223 subjects free of psychiatric illness. The results showed that one coding-synonymous polymorphism (rs3748962, Val1065Val) was in genotypic (p = 0.0027) and allelic (p = 0.0007) association with schizophrenia. In comparison with subjects of the rs3748962-TT type, those of the rs3748962-CT and rs3748962-CC types were at 1.74- and 2.64-fold greater risk of schizophrenia (CT vs. TT: OR = 1.71 (95% CI = 1.15–2.53), p = 0.0014; CC vs. TT: OR = 2.64 (95% CI = 1.37–5.23), p = 0.0047), which supports the hypothesis of an additive model of transmission (p = 0.0006). Furthermore, the frequency of haplotype ATC of rs3791709–rs2289086–rs3748962 was found to be significantly higher in the patients with schizophrenia than in the controls (case vs. control = 36.0% vs. 24.4%, permutation p-value = 0.0002). The findings support the involvement of the ERBB4 gene in schizophrenia in Han Chinese.     

Different implication of NEDD9 genetic variant in early and late-onset Alzheimer's disease

Alzheimer's disease (AD) is a complex and multifactorial progressive neurodegenerative disease. Recently, two studies reported inconsistent results on a possible involvement of the NEDD9 (neural precursor cell expressed, developmentally down-regulated 9, 6p25-p24) as a candidate gene for the risk of developing AD and/or Parkinson's disease (PD). We analyzed the distribution of the rs760678 SNP polymorphism in 735 Italian subjects: 214 unrelated sporadic late-onset AD patients (LOAD, 64.5% females, mean age-at-onset 71.8 ± 5.2 years), 135 early-onset AD patients (EOAD, 57.3% females, mean age-at-onset 57.5 ± 5.5 years) and 386 healthy controls (68.9% females, mean age 83.4 ± 17.9 years; SD). We observed a statistically significant difference between LOAD patients and controls according to genotypes (P = 0.016) and allele frequency (P = 0.007); CC genotype was more frequent in LOAD cases (44.4%) than controls (36.0%). No difference after stratification of the data in terms of gender and status of the APOE ?4 allele was observed. In conclusion, our data do support an implication of the NEDD9 allelic variant in late-onset AD, with an independent effect of the apolipoprotein E (APOE) ?4 allele in the risk of developing AD.     

Alleles and genotypes of polymorphisms of IL-18, TNF-α and IFN-γ are associated with a higher risk and severity of hepatocellular carcinoma (HCC) in Brazil

Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver. We evaluated the association of alleles and genotypes of polymorphisms of IL-18 (-607C/A and -137G/C), IFN-γ (+874T/A) and TNF-α (-238G/A and -308G/A) with the risk and severity of HCC. One-hundred-and-twelve patients with HCC and 202 healthy controls were studied. Single nucleotide polymorphisms (SNPs) were amplified by PCR with specific primers and the products were submitted to polyacrylamide gel electrophoresis and stained with silver. We evaluated tumor presentation, tumor size and presence of metastasis. Significant higher risk of HCC was associated with: alleles IL-18 -607^∗A (P = 0.0235; OR = 1.48; 95%CI = 1.06–2.08); TNF-α -238^∗A (P = 0.0025; OR = 2.12; 95%CI = 1.32–3.40) and TNF-α -308^∗A (P = 0.0351; OR = 1.82; 95%CI = 1.07–3.08); and genotypes IL-18–607AA (P = 0.0048; OR = 3.03; 95%CI = 1.40–6.55); TNF-α -238GA (P = 0.0011; OR = 2.44; 95%CI = 1.45–4.12); and TNF-α -308GA (P = 0.0031; OR = 2.51; 95%CI = 1.39–4.51). Significant association was found between multinodular HCC and IL-18 -607^∗C allele (P = 0.029; OR = 2.40, 95%CI: 1.09–5.28), and IL-18 -607CC genotype (P = 0.028; OR = 3.5, 95%CI: 1.24–9.86). Diffuse HCC was significantly associated with IFN-γ +874TA genotype (P = 0.044; OR = 3.6, 95%CI: 1.03–12.47). The IL-18 -137^∗C allele showed a significant association with the presence of metastasis. Thus, IL-18 -607^∗A and TNF-α (-238^∗A and -308^∗A) alleles may confer susceptibility to HCC, while IL-18 -607^∗C and -137^∗C alleles more severe disease.     

Association between two single nucleotide polymorphisms of PDCD6 gene and increased endometriosis risk

Programmed cell death 6 (PDCD6), a calcium binding protein of the penta EF-hand protein family, and its receptors are involved in regulation of apoptosis pathways. To evaluate the relationship between genetic polymorphisms of PDCD6 gene and endometriosis (ED) risk, we investigated the association of two single nucleotide polymorphisms (SNPs) of PDCD6 gene (rs4957014 and rs3756712) in 220 endometriosis patients and 386 unrelated healthy controls. The genotypes of these two SNPs were determined by using polymerase chain reaction (PCR)–restriction fragment length polymorphism (RFLP) and DNA sequencing methods. Significantly increased endometriosis risk was observed to be associated with G allele of rs4957014 locus (OR = 1.31, 95% CI = 1.03–1.69). We have also observed increased ED risk was statistically associated with rs4957014 polymorphism in a dominant model (OR = 1.52, 95% CI = 1.09–2.13). Although no association has been found between ED risk and the allele frequencies of rs3756712 locus (a marginal P = 0.066, OR = 1.27, 95% CI = 0.98–1.65), but in a dominant model, increased endometriosis risk was significantly associated with rs3756712 polymorphism (OR = 1.54, 95% CI = 1.11–2.17). In conclusion, the current study indicates that PDCD6 gene may be a new susceptibility gene to endometriosis.     

No association between IL-1RN VNTR and the risk of duodenal ulcer: A meta-analysis

The aim of this study was to perform a meta-analysis to investigate a more authentic association between interleukin-1 RN variable number of tandem repeats (IL-1RN VNTR) and duodenal ulcer (DU). Systematic searches of electronic databases Embase, PubMed and Web of Science were performed. Statistical analyses were conducted using software Stata 11.0. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were applied. Publication bias was tested by Begg’s funnel plot and Egger’s regression test. A total of 16 studies including 2115 cases and 3622 controls were included in our final meta-analysis. There was no evidence of significant association between IL-1RN VNTR and DU (allelic model: OR = 1.04, 95%CI = 0.87–1.26; additive model: OR = 0.85, 95%CI = 0.62–1.16; dominant model: OR = 1.06, 95%CI = 0.92–1.23; and recessive model: OR = 0.83, 95%CI = 0.61–1.12). Significant protective associations were found in additive model (OR = 0.51, 95%CI = 0.31–0.83) and recessive model (OR = 0.45, 95%CI = 0.28–0.73) in Caucasian subgroup. In conclusion, our meta-analysis suggests that there is no evidence of significant association between IL-1RN VNTR and DU with or without Helicobacter pylori infection in overall population, whereas significant association is found by subgroup analyses which showed protective effect of IL-1RN allele 2 against DU risk in Caucasian population.     

Sphingosine-1-phosphate acting via the S1P₁ receptor is a downstream signaling pathway in ceramide-induced hyperalgesia

Interleukin-6 (IL-6), identified as a pleiotropic inflammatory cytokine, plays important roles in the acute inflammatory response and in the modulation of the neuroimmune response. To date, large amounts of epidemiological studies have been performed to investigate the association between the IL-6 −174G/C polymorphism and Alzheimer's disease (AD) risk. Inconclusive results, however, have been reported. We aimed to assess the effect of the IL-6 −174G/C polymorphism on AD susceptibility with the use of a meta-analysis. 14 studies involving 3769 cases of AD and 9431 control subjects were identified by a search of Pubmed, Embase and ISI Web of Science databases. Crude odds ratios (ORs) with 95% confidence intervals (CIs) for the IL-6 −174G/C polymorphism and AD risk were computed using fixed- or random-effects model when appropriate. Obvious heterogeneity among studies was detected, and a borderline statistically significant association was observed between the IL-6 −174G/C polymorphism and AD risk in Caucasians (GG vs. CC: OR = 1.35, 95%CI, 1.06-1.72; GG/GC vs. CC: OR = 1.27, 95%CI, 1.05-1.53, respectively). After exclusion of one study, the heterogeneity disappeared and no significant association was observed between the polymorphism and AD risk. These findings indicate that the IL-6 −174G/C polymorphism may not be an independent risk factor for the development of AD.