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.     

Peroxisome proliferator-activated receptor-γ2 Pro12Ala polymorphism is associated with reduced risk for ischemic stroke with type 2 diabetes

Peroxisome proliferator-activated receptor (PPAR)-γ2 has important effects to insulin sensitivity, atherosclerosis, inflammation and endothelial cell function. Through these effects, PPAR-γ2 might be involved with the ischemic stroke in type 2 diabetes. To determine the role of PPAR-γ2 in genetic susceptibility to ischemic stroke in type 2 diabetes, we genotyped 302 ischemic stroke patients, 283 healthy controls and 141 type 2 diabetic patients without ischemic stroke (diabetes duration >10 years) for PPAR-γ2 Pro12Ala polymorphism by polymerase chain reaction-restriction fragment length polymorphism methods. PPAR-γ2 Pro/Ala genotype were lower in ischemic stroke patients than those observed in the control group (4.0% vs. 9.9%, OR = 0.38, P = 0.0046), and it were associated with the incidence of ischemic stroke in the multivariate analysis (OR = 0.43, P = 0.025). Genotypic analysis revealed that ischemic stroke patients with type 2 diabetes displayed a great lower prevalence of the Pro/Ala genotype (2.3%) than controls (9.9%) (OR = 0.21, P = 0.0047). And Pro/Ala genotype of type 2 diabetes patients with ischemic stroke were lower than type 2 diabetes patients without ischemic stroke (2.3% vs. 8.5%, OR = 0.25, P = 0.0321), however the significant association with ischemic stroke was not detected in the multivariate analysis (OR = 0.27, P = 0.051). These results suggest that the Pro/Ala genotype of PPAR-γ2 Pro12Ala polymorphism may be associated with reduced risk for ischemic stroke, and the possibility that it might have a protective effect for ischemic stroke with type 2 diabetes.     

Association of CTLA-4 variants with susceptibility to inflammatory bowel disease: A meta-analysis

Objective

The aim of this study was to determine whether CTLA-4 gene variants were associated with susceptibility to inflammatory bowel disease (IBD).

Methods

Meta-analysis was conducted on the association between CTLA-4 variants and IBD using: (1) allelic contrast, (2) the recessive model, and (3) the dominant model.

Results

A total of 9 relevant studies including 1739 Crohn’s disease (CD) cases, 10 relevant studies containing 1017 ulcerative colitis (UC) cases and 2685 healthy controls were involved in this meta-analysis. Overall, CTLA-4+49A/G, −318C/T and CT60 variants were not associated with IBD susceptibility in all genetic models (P > 0.05). Stratification by ethnicity indicated a significant association between the CTLA-4+49A/G variant and CD in Caucasian group (GG vs. GA + AA: OR = 0.723, 95% CI = 0.564–0.926, P = 0.010). In Asian group, meta-analysis showed a significant association between the CTLA-4 CT60 variant and UC (AA vs. AG + GG: OR = 0.375, 95% CI = 0.163–0.861, P = 0.021).

Conclusions

Based on the published literature, this meta-analysis suggests that the CTLA-4+49A/G variant may be related to CD susceptibility in Caucasians, and the CTLA-4 CT60 variant may be associated with UC susceptibility in Asians.     

NEDD9 rs760678 polymorphism and the risk of Alzheimer's disease: A meta-analysis

The NEDD9 rs760678 polymorphism has been extensively investigated for association to Alzheimer's disease (AD), however, results of different studies have been inconsistent. The objective of this study is to assess the relationship of NEDD9 rs760678 polymorphism and AD risk by using meta-analysis. Systematic searches of electronic databases Pubmed and Embase, as well as hand searching of the references of identified articles were performed. Statistical analyses were performed using software Revman 4.2 and STATA 11.0. A total of 4436 cases and 4420 controls in 11 case–control studies were included. The results indicated that the homozygote GG had a 13% decreased risk of AD, when compared with the C allele carriers (CC + CG) (OR = 0.87, 95%CI = 0.77–0.99, P = 0.04 for GG vs. CG + CC). In the subgroup analysis by ethnicity, significant decreased risk was associated with homozygote GG or G allele carriers in Caucasians (OR = 0.84, 95%CI = 0.74–0.96, P = 0.008 for GG vs. CG + CC; OR = 0.79, 95%CI = 0.69–0.91, P = 0.001 for GG vs. CC; OR = 0.90, 95%CI = 0.84–0.96, P = 0.002 for G vs. C), but not in Asians. This meta-analysis suggests that the GG genotype of NEDD9 rs760678 polymorphism would be a protective factor for AD in Caucasians but not in Asians. To further evaluate the effect of gene–gene and gene–environmental interactions between NEDD9 rs760678 polymorphism and the risk of AD, more studies with larger number of subjects are required.     

Association of the CR1 polymorphism with late-onset Alzheimer's disease in Chinese Han populations: A meta-analysis

It is well known that genetic variants play a critical role in the pathogenesis of Alzheimer's disease (AD). In 2009, a genome-wide association study (GWAS) demonstrated that a single nucleotide polymorphism (SNP), rs6656401, in complement receptor 1 (CR1) is significantly associated with late-onset Alzheimer's disease (LOAD) in Caucasian population. Subsequently, other researchers have attempted to validate this finding in Chinese Han populations. However, these findings in Chinese Han populations have produced both negative and positive results. To derive a more precise estimation for the relationship, we performed the present meta-analysis by analyzing three published association studies involving CR1 SNP rs6656401 through the use of the RevMan (v.5.1) program. Pooled odds ratios (ORs) were calculated for allele contrasts (A vs. G) and a dominant model [(AA + AG) vs. GG] in three studies that included 1019 cases and 1080 controls, respectively. The statistical results showed a significant difference between patients and controls for the A allele of CR1 SNP rs6656401 (P = 0.005). In addition, carriers of the A allele (AA + AG) of rs6656401 had a 1.69-fold increased risk for LOAD compared with non-carriers (GG) (P = 0.01). In conclusion, despite there are some limitations, this meta-analysis indicates that the A allele of the CR1 SNP rs6656401 is significantly associated with LOAD susceptibility in Chinese Han populations.     

Association between 1425G/A SNP in PRKCH and ischemic stroke among Chinese and Japanese populations: a meta-analysis including 3686 cases and 4589 controls

Aims: Meta-analysis was performed to investigate the association between 1425G/A SNP in PRKCH (the gene encoding for protein kinase C η) and ischemic stroke among Chinese and Japanese populations. Methods: The databases of MEDLINE, PubMed, Chinese Biomedical Database, China National Knowledge Infrastructure, and WANFANG DATA until September 2011 were searched for published case-control studies on 1425G/A SNP in PRKCH and ischemic stroke. Strict selection criteria and exclusion criteria were determined, and pooled odds ratio (OR) and the 95% confidence interval (CI) were calculated using a fixed or random effects model to determine the strength of the genetic association. The publication bias was further evaluated by calculating the fail-safe number in the included studies. Results: Five studies, comprising 3686 cases and 4589 controls, passed all the criteria and therefore were included in the meta-analysis. Test for heterogeneity showed that P values (P = 0.76, 0.24, respectively) in the two meta-analyses were both greater than 0.05, therefore the fixed effects model was performed. Statistically significant association between 1425G/A SNP in PRKCH and ischemic stroke was identified (OR = 1.34; 95% CI, 1.22-1.47), and the association was even stronger between 1425G/A SNP in PRKCH and lacunar infarction (OR = 1.44; 95% CI, 1.28-1.63). The fail-safe number (N_{fs 0.05}) for 1425G/A SNP in PRKCH with ischemic stroke and lacunar infarction was 59 and 44, respectively, which were greater than the number of studies included in the analyses. Conclusions: SNP 1425G/A in PRKCH was associated with ischemic stroke, particularly lacunar infarction, in Chinese and Japanese populations. More studies of different subtypes of stroke need to be done to confirm the results in other Asian populations.     

A meta-analysis about the association between −1082G/A and −819C/T polymorphisms of IL-10 gene and risk of type 2 diabetes

The present meta-analysis was conducted to investigate the association between the −1082G/A and −819C/T polymorphisms of the IL-10 gene and risk of type 2 diabetes mellitus (T2DM). Relevant articles were identified by searching PubMed, Embase, and Web of Science. Pooled odds ratios (ORs) were used to assess the strength of the association between target polymorphisms and the risk of T2DM. Significant associations between the −1082G/A polymorphism and T2DM were found for the allele contrast (OR = 0.90, 95% CI: [0.83, 0.98], P = 0.02), homozygote contrast (OR = 0.82, 95% CI: [0.69, 0.97], P = 0.02), and recessive genetic model (OR = 0.85, 95% CI: [0.74, 0.96], P = 0.01). However, no significant association was found for the dominant genetic model (OR = 0.91, 95% CI: [0.80, 1.05], P = 0.08). The association between −819C/T polymorphism and T2DM was significant for the allele contrast (OR = 0.73, 95% CI: [0.64, 0.84], P < 0.01); however, no significant associations were found for −819C/T in the homozygote contrast (OR = 1.01, 95% CI: [0.38, 2.67], P = 0.99), dominant genetic model (OR = 0.94, 95% CI: [0.50, 1.77], P = 0.86), and recessive genetic model (OR = 0.92, 95% CI: [0.50, 1.68], P = 0.78). No significant publication bias was detected. This meta-analysis suggests that allele A of −1082G/A and allele C of −819C/T in the IL-10 gene have potentially protective effects in terms of risk of T2DM.     

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.     

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.     

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.     

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.     

The association of CTLA‐4 A49G polymorphism with colorectal cancer risk in a Chinese Han population

Cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) is expressed in T cells and plays an important role in the regulation of T cell. CTLA‐4 has long been considered to be associated with various kinds of diseases. With the attempt to examine the association between CTLA‐4 A49G polymorphism and colorectal cancer risk in a Chinese Han population, we employed TaqMan assay to genotype the CTLA‐4 A49G polymorphism in 311 colorectal cancer cases and 389 cancer‐free controls. We found evidence of the association between CTLA‐4 A49G polymorphism and colorectal cancer risk (GG vs. AA: OR = 2.01, 95% CI = 1.29–3.07, P = 0.002; GA vs. AA: OR = 2.32, 95% CI = 1.53–3.57, P = 0.001; GA + GG vs. AA: OR = 2.16, 95% CI = 1.46–3.21, P = 0.001). Next, we performed a meta‐analysis to comprehensively examine the association between CTLA‐4 A49G polymorphism and colorectal cancer risk. We found a significant association between CTLA‐4 A49G polymorphism and colorectal cancer risk among Asians, which is consistent with our result. However, we found no evidence for the association between CTLA‐4 A49G polymorphism and colorectal cancer risk among Caucasians. In conclusion, we demonstrated that the CTLA‐4 A49G polymorphism increased the susceptibility of colorectal cancer in Asian population.     

Microtubule-associated protein tau (MAPT) influences the risk of Parkinson's disease among Indians

Parkinson's disease (PD) is a neurodegenerative disease of the central nervous system and its prevalence increases with age. Microtubule-associated protein tau (MAPT), a neuronal protein is involved in the pathogenesis of several neurodegenerative diseases including PD. To determine the broader significance of this association with PD, replicative studies in distinct ethnic populations are required. In this study, we investigated MAPT for its potential association with PD using five haplotype-tagging SNPs and the del-In9 polymorphism of MAPT in 301 PD patients and 243 healthy controls from eastern India. Our case–control analysis did not show a significant association with any of the markers and PD. However, a risk haplotype [GAC + G] for PD was identified (OR = 1.563; 95% CI = 1.045–2.337; p = 0.03). In addition, haplotype AAC + A (OR = 2.787; 95% CI = 1.372–5.655; p = 0.004) was strongly associated with early onset PD (age at onset ≤40 years) and AAC + G haplotype showed a weak association (OR = 2.233; 95% CI = 1.018–4.895; p = 0.045) with late onset PD (age at onset >40 years). This observation highlights the significance of rs7521 in modifying the age at onset of PD under a common haplotype background. We also identified AGC + A as a risk haplotype for sporadic cases (OR = 2.773, 95% CI = 1.198–6.407, p = 0.016). This is the first association study from India conducted on MAPT among PD patients and provides valuable information for comparison with other ethnic groups.     

Vascular endothelial growth factor gene polymorphisms and vasculitis susceptibility: A meta-analysis

Objective

The aim of this study was to explore whether vascular endothelial growth factor (VEGF) polymorphisms are associated with susceptibility to vasculitis.

Methods

Meta-analyses were conducted on the associations between the −634 C/G, +936 C/T, −1154 A/G, and −2578 A/C polymorphisms of VEGF and vasculitis.

Results

Eight studies on VEGF polymorphisms and vasculitis involving 2740 subjects (vasculitis 834, controls 1906) were included in this meta-analysis. The meta-analysis showed no association between vasculitis and the VEGF −634 C allele (OR = 1.161, 95% CI = 0.921–1.464, p = 0.207) among study subjects. Meta-analysis showed no association between vasculitis and the VEGF + 936 T allele (OR = 1.121, 95% CI = 0.905–1.390, p = 0.295). However, stratification by ethnicity indicated a significant association between the VEGF + 936 T allele and vasculitis in Europeans, but not in Asians (OR = 1.486, 95% CI = 1.038–2.128, p = 0.030; OR = 0.958, 95% CI = 0.773–1.253, p = 0.755). Meta-analysis showed no association between vasculitis and the VEGF −1154 A/G and 2578 A/C polymorphisms.

Conclusions

This meta-analysis suggests that the VEGF + 936 T allele is associated with susceptibility to vasculitis in Europeans, but not in Asians.     

Polymorphisms in thymic stromal lymphopoietin gene demonstrate a gender and nasal polyposis-dependent association with chronic rhinosinusitis

Background

Recent studies have suggested that thymic stromal lymphopoietin (TSLP), a key cytokine involved in the dendritic cell-mediated activation of Th2-mediated inflammatory responses, is significantly increased in nasal polyps from atopic individuals. Our objective was therefore to explore firstly any associations between single nucleotide polymorphisms (SNPs) in and around the TSLP gene and development of chronic rhinosinusitis (CRS; with (CRSwNP) or without (CRSsNP) nasal polyps and, and secondly the influence of nasal polyposis and gender.

Methods

A population-based case-control association analysis was performed in a Han Chinese cohort. DNA extracted from peripheral blood leukocytes from 638 subjects with CRS (306 CRSwNP and 332 CRSsNP) and 325 healthy controls was assessed for 11 SNPs in and around TSLP gene, selected from the Chinese HapMap genotyping dataset. Genetic association tests were performed using the Haploview and STATA software package.

Results

Single-locus analysis of CRS risk, showed no significant differences in allele or genotype frequencies between CRS subjects and controls. Stratified analyses of association between the selected SNPs and CRS adjusted for gender demonstrated that rs13156068 (CC genotype: P = 0.010, OR = 0.289) and rs764917 (CC genotype: P = 0.040, OR = 0.509) were significantly protective against CRS, whereas rs6886755 (GT genotype: P = 0.040, OR = 0.509) presented a risk among females. In contrast, rs764917 (CA genotype: P = 0.033, OR = 1.553) presented risk for CRS in males. Furthermore, SNPs rs252706 (AA genotype: P = 0.012, OR = 0.552) and rs764917 (CA genotype: P = 0.001, OR = 0.182) displayed protective roles among CRSwNP, but not CRSsNP, subjects.

Conclusions

This study suggests that SNPs in TSLP gene may exert a gender and/or nasal polyposis-dependent risk for development of CRS in Chinese subjects.     

Toll-like receptor 4 gene Asp299Gly polymorphism in myocardial infarction: A meta-analysis of 15,148 subjects

It remains controversial regarding the association between toll-like receptor 4 (TLR4) gene Asp299Gly (+896 A/G) polymorphism and myocardial infarction (MI) risk. Thus, a large-scale meta-analysis evaluating the potential association between this gene variant and MI risk is required. PubMed, Embase, Web of Science, CBMdisc, CNKI, and Google Scholar were searched until February 6, 2013. All the statistical tests were performed using Stata 11.0. Nine articles involving 10 studies were included in the final meta-analysis, covering a total of 8299 MI cases and 6849 controls. Overall, no significant association was found between the TLR4 gene Asp299Gly polymorphism and MI risk (G allele vs. A allele: OR = 0.95, 95% CI = 0.74–1.22, p = 0.71; G/G vs. A/A: OR = 1.03, 95% CI = 0.54–1.98, p = 0.93; G/G vs. A/G + A/A: OR = 1.05, 95% CI = 0.55–2.03, p = 0.87; G/G + A/G vs. A/A: OR = 0.92, 95% CI = 0.75–1.13, p = 0.42). In the subgroup analysis based on source of controls, there was also lack of evidence for significant association between the TLR4 gene Asp299Gly polymorphism and MI risk. In summary, the present meta-analysis indicated that the TLR4 gene Asp299Gly polymorphism was not associated with MI 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.     

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 insulin gene variable number of tandem repeats regulatory polymorphism with polycystic ovary syndrome

The present meta-analysis aimed to investigate the association between insulin gene variable number of tandem repeats (INS VNTR) and polycystic ovary syndrome (PCOS). Systematic searches of electronic databases, reference lists of included articles, and the abstracts presented at related scientific societies meetings 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 9 studies including 1075 PCOS patients and 2878 controls were included in the meta-analysis. There were evidence of statistical significant association between INS VNTR and PCOS in allelic model (OR = 1.25, 95% CI = 1.08–1.43, P = 0.002) and dominant model (OR = 1.34, 95% CI = 1.11–1.63, P = 0.003) but not in additive model (OR = 1.38, 95% CI = 0.93–2.04, P = 0.11) and recessive model (OR = 1.26, 95% CI = 0.96–1.65, P = 0.09). No significant publication bias was shown by funnel plots and Egger’s regression tests. In conclusion, our meta-analysis suggests that the III allele of INS VNTR is associated with increased risk of PCOS.     

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.