Association between human leukocyte antigen-G 14-bp insertion/deletion polymorphism and cancer risk: A meta-analysis and systematic review

Background

Human leukocyte antigen-G (HLA-G) is involved in the development and progression of human cancers, and numerous molecular epidemiological studies have been conducted to explore the potential relationship of HLA-G 14-bp insertion/deletion (ins/del) polymorphism with cancer risk. However, results from published studies were inconclusive.

Methods

Both PUBMED and EMBASE databases were searched comprehensively to identify eligible studies investigating the association of HLA-G 14-bp ins/del polymorphism with cancer risk. Statistical analysis was performed by using STATA 12.0 and Review Manager 5.0.

Results

Fourteen eligible studies with 2340 cancer patients and 3967 controls were included and analyzed with odds ratio (OR) and its corresponding 95% confidence interval (CI). Overall, no significant association between HLA-G 14-bp ins/del polymorphism and overall cancer risk was detected in all comparison models. Further subgroup analyses based on ethnicity and cancer types demonstrated the significant association among Asians (ins/del vs. del/del: OR = 0.80, 95% CI, 0.66–0.95; ins/ins + ins/del vs. del/del: OR = 0.80, 95% CI, 0.65–0.97) and for breast cancer (ins allele vs. del allele: OR = 0.76, 95% CI, 0.61–0.96; ins/ins vs. del/del: OR = 0.57, 95% CI, 0.37–0.87; and ins/ins vs. ins/del + del/del: OR = 0.60, 95% CI, 0.42–0.87).

Conclusion

This study suggested that HLA-G 14-bp ins/del polymorphism might contribute to breast cancer susceptibility and overall cancer risk among Asians. Further well-designed studies with larger sample size are warranted to validate our conclusion.     

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.     

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.     

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.     

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.     

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.     

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.     

Human leukocyte antigen G is associated with esophageal squamous cell carcinoma progression and poor prognosis

Human leukocyte antigen G (HLA-G) is a non-classical HLA class I molecule thought to play a key role in maternal-fetal tolerance and cancer immune evasion. This study aimed to investigate the HLA-G expression in lesion sections and plasma sHLA-G levels of primary esophageal squamous cell carcinoma (ESCC) patients and its clinical significance in diagnosis and prognosis of ESCC. 60 ESCC patients and 28 healthy controls were recruited, and the positive expression of HLA-G in ESCC lesions and adjacent normal tissues were 70% (42/60) and 8.6% (5/60) (P < 0.05), respectively, while no expression was found in normal controls. HLA-G1 and HLA-G5 were determined to be dominating isoforms measured by RT-PCR. There was a significant difference in plasma sHLA-G levels between patients with ESCC (15.04 U/ml, range 4.33–250.00 U/ml) and healthy controls (6.81 U/ml, range 0–29.27 U/ml) (P < 0.01). The plasma IL-10 level was higher in ESCC patients than the controls (23.86 pg/ml vs. 12.81 pg/ml, P < 0.01). HLA-G expression in lesion tissues was correlated with cancer cell differentiation (P = 0.033), lymph node metastasis (P = 0.035) of ESCC. However, no obvious correlations were demonstrated between the plasma sHLA-G levels and the clinicopathological parameters. There was a significant correlation between sHLA-G and IL-10 expression (r = 0.353, P = 0.006) in patients with Esophageal squamous cell carcinoma. HLA-G positive expression showed poorer prognosis of ESCC. HLA-G positive expression might serve as a potential marker in the diagnosis or prediction of ESCC.     

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.     

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).     

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.     

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.     

Low producer MBL genotypes are associated with susceptibility to systemic lupus erythematosus in Odisha,India

Variants of MBL gene have been associated with autoimmune disorders. The aim of this study was to explore whether common polymorphisms in MBL gene are associated with susceptibility to systemic lupus erythematosus (SLE) and its clinical manifestations in a cohort from eastern India. A total of 108 female SLE patients and 105 age, sex, and ethnically matched healthy controls were enrolled in the study. MBL2 codon and promoter polymorphisms were genotyped by AS-PCR and dARMS PCR, respectively. Plasma level of MBL was quantified by ELISA. Higher frequency of BB genotype and minor allele (B) was observed in patients of SLE compared to healthy controls (BB genotype: P = 0.0002; OR = 5.75, 95% CI = 2.09–15.76, B allele: P < 0.0001; OR = 2.78, 95% CI = 1.66–4.64). MBL codon 54, H-550L, Y-221X polymorphisms and combined MBL genotypes contributed to plasma MBL levels. Prevalence of MBL low producer genotype (LXA/LYB, LYB/LYB and LXB/LXB) was significantly higher in SLE patients compared to healthy control. (P = 0.005; OR = 3.09, 95% CI = 1.38–6.91). On analysis of clinical manifestations, MBL low producer genotype was significantly associated with autoimmune haemolytic anaemia (P = 0.006; OR = 13.06). Results of the present study indicate MBL2 variants as possible risk factors for development of SLE and clinical manifestation in eastern India.     

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.     

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.     

Associations between interleukin-10 polymorphisms and susceptibility to systemic lupus erythematosus: A meta-analysis

Objective

The study determined whether interleukin-10 (IL-10) polymorphisms confer susceptibility to systemic lupus erythematosus (SLE).

Methods

A meta-analysis was conducted on the associations between the IL-10-1082 G/A, -819 C/T, -592 C/A polymorphisms and the haplotype of the IL-10-1082 G/A, -819 C/T, -592 C/A polymorphisms and SLE.

Results

A total of 19 studies involving 2828 SLE patients and 4008 controls were considered in the meta-analysis. Meta-analysis of the IL-10-1082 G/A polymorphism revealed an association between SLE and the IL-10-1082 G allele (odds ratio [OR] = 1.158, 95% confidence interval [CI] = 1.051–1.276, p = 0.003). Stratification by ethnicity indicated an association between the IL-10-1082 G allele and SLE in Europeans (OR = 1.160, 95% CI = 1.039–1.296, p = 0.008). Meta-analysis stratified by ethnicity produced an association between the IL-10-819 C allele and SLE in Asians (OR = 1.308, 95% CI = 1.030–1.619, p = 0.027). Meta-analysis of the homozygous GCC/GCC haplotype failed to show a significant association with SLE in Europeans (OR = 1.223, 95% CI = 0.981–1.526, p = 0.074). However, meta-analysis of the GCC haplotype revealed a significant association with RA in all study subjects (OR = 1.402, 95% CI = 1.001–1.964, p = 0.049). Stratification by ethnicity indicated an association between the GCC haplotype and SLE in Europeans (OR = 1.656, 95% CI = 1.087–2.523, p = 0.019), but not in Asians (OR = 1.100, 95% CI = 0.703–1.721, p = 0.677). Meta-analysis of homozygous ATA/ATA haplotype failed to show a significant association with SLE in overall and European groups. However, meta-analysis of the ATA haplotype revealed a significant association with SLE in all study subjects (OR = 1.516, 95% CI = 1.039–2.213, p = 0.031) and Asians (OR = 2.580, 95% CI = 2.086–3.192, p < 1 × 10⁻⁹), but not in Europeans (OR = 1.233, 95% CI = 0.816–1.862, p = 0.320).

Conclusions

This meta-analysis suggests that the IL-10 polymorphisms confer susceptibility to SLE in Europeans and in Asians.     

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.     

Associations between interleukin 1 polymorphisms and susceptibility to systemic lupus erythematosus: A meta-analysis

Objective

This study determined whether interleukin 1 (IL1) polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE).

Methods

A meta-analysis was conducted on the associations between the IL1A, IL1B, and IL1 receptor antagonist (IL1RN) polymorphisms and SLE.

Results

A total of 15 studies involving 1956 SLE cases and 2347 controls were included in the meta-analysis. The meta-analysis showed an association between SLE and the IL1A −889 T allele in the overall population and Europeans (OR = 0.858, 95% CI = 0.737–0.986, p = 0.032; OR = 0.827, 95% CI = 0.687–0.994, p = 0.043). Meta-analysis of the IL1RN polymorphism revealed an association with SLE in all study subjects (OR for IL1RN^∗2 = 1.539, 95% CI = 1.266–1.871, p = 1.5 × 10⁻²) and in Europeans and Asians (OR = 1.483, 95% CI = 1.187–1.852, p = 0.001; OR = 1.787, 95% CI = 1.167–2.736, p = 0.008). No associations were found between SLE and the IL1B −511 C/T, 3953 C/T, and IL1A +4845 G/T polymorphisms.

Conclusions

This meta-analysis suggests IL1A −889 C/T polymorphism is associated with susceptibility to SLE in Europeans, and that the IL1RN^∗2 allele is associated with susceptibility to SLE in Europeans and Asians.     

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.     

14-bp ins/del polymorphism and +3142C>G SNP of the HLA-G gene have a significant impact on acute rejection after liver transplantation

Expression of human leukocyte antigen G (HLA-G) has been associated with increased graft survival and decreased rejection episodes. It has been described that the HLA-G 14-base pair (bp) insertion/deletion (ins/del) (rs66554220) and +3142C>G (rs1063320) gene polymorphisms modify the expression level of HLA-G. The aim of the study was to investigate whether these HLA-G polymorphisms have an impact on acute rejection after liver transplantation. In total, 146 liver transplant recipients (57 with acute rejection and 89 without acute rejection) and 99 corresponding liver donors were genotyped for both polymorphisms. In liver transplantation the 14-bp ins/ins and the +3142GG genotypes are more frequent in recipients without rejection compared to recipients with rejection (3.5% vs. 31.5%, p = <0.001; 12.3% vs. 41.6%, p = <0.001) demonstrating an association with protection from acute rejection. In contrast, in liver donors we could not reveal an association. We conclude that 14-bp ins/ins and +3142GG genotypes of HLA-G in liver transplant recipients are of importance for prediction of acute rejection after liver transplantation. Thus genotyping of liver recipients for both polymorphisms might be useful to stratify liver transplant recipients according to the risk of acute liver transplant rejection.