Association of interleukin-1 gene polymorphisms with multiple sclerosis: a meta-analysis

Background

Dysregulated levels of interleukin-1 (IL-1) were observed in patients with multiple sclerosis (MS). Previous studies have provided conflicting evidence implicating the IL-1 gene polymorphisms in MS risk.

Methods

A meta-analysis of 16 case–control studies involving 3,482 cases and 3,528 controls was conducted to evaluate this association.

Results

No association was found between the IL-1α ?889 (rs1800587), IL-1α +4,845 (rs17561), IL-1β ?511 (rs16944), IL-1β +3,953 (rs1143634), IL-1ra variable number tandem repeat (VNTR) polymorphisms and MS risk. However, in subgroup analyses for the IL-1ra VNTR polymorphism, we found that individuals carrying the 2 allele had a 32 % increased risk for bout-onset MS (relapsing remitting and secondary progressive MS) when compared to the LL homozygotes (OR = 1.32, 95 % CI = 1.06–1.66, P _z = 0.014).

Conclusion

Common variants in the IL-1 region are not associated with MS risk but our data suggest that the IL-1ra VNTR polymorphism might be associated with bout-onset MS subtype.     

Interleukin-18 promoter polymorphisms and plasma levels are associated with increased risk of periodontitis: a meta-analysis

Objective

Emerging evidence has showed that interleukin-18 (IL-8) promoter polymorphisms and plasma IL-18 levels may be associated with increased risk of periodontitis, but individually published results are inconclusive. The aim of this meta-analysis was to derive a more precise estimation of these associations.

Methods

A literature search of PubMed, Cochrane Library, Embase, Web of Science, SpringerLink, China BioMedicine and China National Knowledge Infrastructure databases was conducted on articles published before April 1st, 2013. Crude odds ratio (OR) or standardized mean difference (SMD) with 95 % confidence intervals (CI) were calculated.

Results

Nine case–control studies were included with a total of 576 periodontitis patients and 458 healthy controls. Two common polymorphisms (?607A > C and ?137G>C) in the IL-18 gene were addressed. Our meta-analysis results indicated that the C variant of IL-18 ?607A>C polymorphism was associated with increased periodontitis risk (C allele vs. A allele: OR = 1.86, 95 % CI: 1.30–2.65, P = 0.001; AC+CC vs. AA: OR = 2.64, 95 % CI: 1.34–5.21, P = 0.005). There was also a significant association between the C variant of IL-18 ?137G>C polymorphism and an increased periodontitis risk (C allele vs. G allele: OR = 1.47, 95 % CI: 1.13–1.91, P = 0.004; GC+CC vs. GG: OR = 1.66, 95 % CI: 1.21–2.29, P = 0.002). Furthermore, the mean levels of plasma IL-18 of periodontitis patients were also higher than those of healthy controls (SMD = 1.18, 95 % CI: 0.51–1.85, P = 0.001).

Conclusion

The current meta-analysis suggests that IL-18 promoter polymorphisms and plasma IL-18 levels are associated with increased risk of periodontitis. IL-18 promoter polymorphisms and elevated plasma IL-18 levels may be useful biomarkers for predicting the development of periodontitis.     

Associations between PTPN2 polymorphisms and susceptibility to ulcerative colitis and Crohn’s disease: a meta-analysis

Objective

Ulcerative colitis (UC) and Crohn’s disease (CD) result from an interaction between genetic and environmental factors. Though several polymorphisms have been identified in PTPN2, their roles in the incidence of UC and CD are conflicting. This meta-analysis was aimed to clarify the impact of these polymorphisms on UC and CD risk.

Method

PubMed, EMBASE, Cochrane Library and CBM were searched until 23 July 2013 for eligible studies on three PTPN2 polymorphisms: rs2542151, rs1893217 and rs7234029. Data were extracted, and pooled odd ratios (ORs) as well as 95 % confidence intervals (95 % CIs) were calculated.

Conclusion

The meta-analysis indicated that rs2542151, rs1893217 and rs1893217 were associated with increased CD risk, while the former was associated with increased UC risk. The differences in age of onset and ethnic groups may influence the associations. Gene–gene and gene–environment interactions should be investigated in the future.

Results

Seventeen studies with 18,308 cases and 20,406 controls were included. Significant associations were found between rs2542151 polymorphism and CD susceptibility (OR = 1.22, 95 % CI, 1.15–1.30, I ² = 32 %), as well as between rs2542151 and UC susceptibility (OR = 1.16, 95 % CI, 1.07–1.25, I ² = 39 %). A similar result was found in Caucasians, but not in Asians. Moreover, a significant increase in CD risk for all carriers of the minor allele of rs1893217 (OR = 1.45, 95 % CI, 1.23–1.70, I ² = 0 %) and rs7234029 (OR = 1.36, 95 % CI, 1.16–1.59, I ² = 0 %) were found. For children, the rs1893217 polymorphism appeared to confer susceptibility to CD (OR = 1.56, 95 % CI, 1.28–1.89, I ² = 0 %).     

Genetic association between TAP1 and TAP2 polymorphisms and ankylosing spondylitis: a systematic review and meta-analysis

Objectives

Ankylosing spondylitis (AS) is a chronic inflammatory joint disease. The transporter associated with antigen processing (TAP) has been identified to play an important role in immune response as well as the HLA-associated diseases. The aim of our meta-analysis was to investigate the contribution of TAP (TAP1 and TAP2) polymorphisms to the risk of AS.

Methods

Meta-analyses were performed between 2 polymorphisms in TAP1 (TAP1-333, -637) and 3 polymorphisms in TAP2 (TAP2-379, -565, and -665) and AS.

Results

The meta-analyses were involved with 6 studies with 415 cases and 659 controls. Significant association was found between TAP1-333Val, TAP1-637Gly, and TAP2-565Thr and AS compared with combined control group (TAP1-333Val: p = 0.009, OR = 1.40, 95% CI 1.09–1.80; TAP1-637Gly: p = 0.002, OR = 1.48, 95% CI 1.15–1.91; p = 0.03, OR = 1.38, 95% CI 1.04–1.84). Subgroup analysis shown that significant association was only found in AS when compared with HLA-B27-negative controls (TAP1-333Val: p = 0.004, OR = 1.53, 95% CI 1.14–2.06; TAP1-637Gly: p = 0.004, OR = 1.52, 95% CI 1.15–2.02; p = 0.02, OR = 1.56, 95% CI 1.09–2.24), but not in AS when compared with HLA-B27-positive controls (p > 0.05). Moreover, no significant associations were found between haplotypes in TAP1 and TAP2 in both the combined and the subgroup analyses (p > 0.05).

Conclusions

TAP1-333Val, TAP1-637Gly, and TAP2-565Thr were likely to be associated with AS.

     

Human COL5A1 rs12722 gene polymorphism and tendon properties in vivo in an asymptomatic population

Purpose

Gene variants encoding for proteins involved in homeostatic processes within tendons may influence its material and mechanical properties in humans. The purpose of this study was to examine the association between one such gene variant, gene encoding collagen type V alpha 1 chain (COL5A1) rs12722, and patellar tendon dimensions and mechanical properties in vivo.

Methods

Eighty-four recreationally active, Caucasian, men and women, aged 18–39, with no history of injuries to the knee and a body mass index between 18.5 and 30 were recruited. Women were not recruited if they were pregnant or using any form of hormone-based contraception. The COL5A1 rs12722 genotype was determined using real-time polymerase chain reaction. Patellar tendon dimensions (volume) and functional (elastic modulus) properties were assessed in vivo using geometric modelling, isokinetic dynamometry, electromyography and ultrasonography.

Results

After adjustments for non-genetic factors, no significant associations were evident between the COL5A1 rs12722 gene variant and either patellar tendon volume (P = 0.933) or elastic modulus (P = 0.206), nor with a calculated Z score that combined these dimensional and functional properties into a composite value (P = 0.647). Similarly, no association was evident when comparing individuals with/without the rare C allele (volume, P = 0.883; elastic modulus, P = 0.129; Z score, P = 0.631).

Conclusions

Tendon properties do not seem to be influenced by the COL5A1 rs12722 gene variant. Although the COL5A1 rs12722 polymorphism has previously been associated with the risk of tendon pathology, that association is unlikely to be mediated via underlying tendon dimensional and functional properties.     

The <Emphasis Type="Italic">NLRP3</Emphasis> and <Emphasis Type="Italic">CASP1</Emphasis> gene polymorphisms are associated with developing of acute coronary syndrome: a case-control study

The protein products of NLRP3 and CASP1 genes are involved in the cleavage of pro-IL-1B and pro-IL-18 leading to the active cytokines, which play an important role in the development of the acute coronary syndrome (ACS). The aim of the present study was to evaluate whether NLRP3 and CASP1 gene polymorphisms are biomarkers of ACS susceptibility in Mexican population. Two polymorphisms of the CASP1 gene [G+7/in6A (rs501192) and A10370-G Exon-6 (rs580253)] and one of the NLRP3 gene [UTR′3 G37562-C (rs10754558)] were genotyped by 5′ exonuclease TaqMan assays in a group of 617 patients with ACS and 609 control individuals. Under recessive model, the CASP1 G+7/in6A polymorphism was associated with an increased risk of developing ACS when compared to healthy controls (OR = 1.76, 95% CI 1.08–2.86, P _Res  = 0.022). In the same way, under recessive model, the CASP1 A10370-G was associated with increased risk of ACS (OR = 1.75, 95% CI 1.07–2.85, P _Res  = 0.025). Moreover, under co-dominant, dominant, over-dominant, and additive models, the NLRP3 UTR′3 G37562-C was associated with a decreased risk of ACS (OR = 0.45, 95%CI 0.22–0.92, P _Co-dom  = 0.006; OR = 0.61, 95%CI 0.44–0.84, P _Dom  = 0.002; OR = 0.67, 95%CI 0.48–0.94, P _Over-dom  = 0.02; and OR = 0.65, 95%CI 0.50–0.94, P _Add  = 0.02, respectively). In summary, this study demonstrates that the G+7/in6A and A10370-G polymorphisms of the CASP1 gene are associated with increased risk of developing ACS, whereas the UTR′3 G37562-C polymorphism of the NLRP3 gene is associated with a decreased risk of developing ACS in Mexican population.     

The <Emphasis Type="Italic">PTPN22</Emphasis> R263Q polymorphism confers protection against systemic lupus erythematosus and rheumatoid arthritis,while <Emphasis Type="Italic">PTPN22</Emphasis> R620W confers susceptibility to Graves’ disease in a Mexican population

Objective

The functional PTPN22 R620W polymorphism (rs2476601) is clearly associated with susceptibility to several autoimmune diseases (ADs). However, the PTPN22 R263Q polymorphism (rs33996649) has been scarcely explored in different ADs. Here we aimed to examine the associations of the PTPN22 R620W and R263Q polymorphisms with susceptibility to or protection against rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Graves’ disease (GD) among Mexican patients.

Methods

We conducted a case–control study including 876 patients (405 with SLE, 388 with RA, and 83 with GD) and 336 healthy control individuals. PTPN22 genotypes were determined using the TaqMan 5′ allele discrimination assay.

Results

PTPN22 R620W was associated with GD susceptibility (OR 4.3, p = 0.004), but was not associated with SLE (OR 1.8, p = 0.19). We previously demonstrated that this polymorphism is associated with RA susceptibility (OR 4.17, p = 0.00036). Moreover, PTPN22 R263Q was associated with protection against SLE (OR 0.09, p = 004) and RA (OR 0.28, p = 0.045), but was not associated with GD.

Conclusions

Our data provide the first demonstration that PTPN22 R620W confers GD susceptibility among Latin-American patients. Moreover, this is the second report documenting the association of PTPN22 R263Q with protection against SLE and RA.

     

Risk factors and outcomes for the acquisition of carbapenem-resistant Gram-negative bacillus bacteremia: A retrospective propensity-matched case control study

Background/purpose

A substantial number of carbapenem-resistant Gram-negative bacilli (CR GNB) have been identified among the etiologic multidrug-resistant GNB in healthcare-associated infections. For achieving a better therapeutic outcome by minimizing inappropriate empirical antibiotic treatment before blood culture and susceptibility testing results are available, it is very important to identify patients who are at risk for the development of CR GNB bacteremia.

Polymorphism rs547984 on human chromosome 1q43 is not associated with primary open angle glaucoma in a Saudi cohort

Background

To investigate the association between polymorphism rs547984, located in close proximity to the Zona Pellucida Glycoprotein 4 (ZP4) gene on human chromosome 1q43 and primary open angle glaucoma (POAG).

Method

Polymorphism rs547984 was genotyped using Taq-Man® assay in 185 subjects comprising of 90 unrelated POAG cases and 95 controls of Saudi origin.

Results

Association analysis between cases and controls revealed no significant genotype distribution under additive (p = 0.356), dominant (p = 0.517) and recessive (p = 0.309) models. Besides, the allele frequency distribution was also found to be non-significant (p = 0.70). The minor “A” allele frequency was found to be 0.49 and 0.50 among POAG cases and controls, respectively. In addition, specific clinical indices used to assess severity of glaucoma such as intraocular pressure (IOP), cup/disc ratio and number of anti-glaucoma medication also did not show any significant genotype distribution in POAG cases.

Conclusion

Polymorphism rs547984 is neither associated with any clinical indices important for POAG such as IOP and cup/disc ratio nor is a risk factor for POAG in the Saudi cohort.

     

Association of genetic polymorphisms in MIF with breast cancer risk in Chinese women

Macrophage migration inhibitory factor (MIF) has been reported to associate with increased cancer risk in several cancers. However, the role of MIF in breast cancer (BC) susceptibility remains unknown. For the first time, we conducted a case–control study to assess the potential association of three common MIF gene variants (rs755622, rs1803976, rs11548059) with BC susceptibility in Chinese women. Total 560 breast cancer patients and 583 age- and sex-matched healthy individuals were recruited from Northwest China, and the DNA was genotyped by Sequenom MassARRAY. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed to estimate the associations. We found that C/G, C/C, and C/G–C/C genotype carriers in MIF rs755622 have a significantly increased risk of BC (C/G vs. G/G: OR = 1.36, 95% CI = 1.07–1.75, P = 0.014; C/C vs. GG: OR = 2.01, 95% CI = 1.06–3.79, P = 0.029; C/G–C/C vs. G/G: OR = 1.42 95% CI = 1.11–1.80, P = 0.004). Further analyses indicate that the BC risk is associated with Ki-67 status, and the rs755622 polymorphism increases breast cancer risk among elder patients (≥49 years). There is no association between BC risk and other two polymorphisms (rs1803976 and rs11548059) by overall analysis and stratified analysis. In conclusion, MIF rs755622 polymorphism increases BC susceptibility in Chinese population, especially among elder patients.     

白介素受体相关激酶-1基因多态性与类风湿关节炎的相关性

目的探讨白介素受体相关激酶-1(IRAK1)rs3027898和rs1059703多态性性与类风湿关节炎(RA)易感性及临床参数的关系。方法收集RA患者123例和体检的220名健康对照者外周血标本,采用聚合酶链反应-连接酶检测反应(PCR-LDR)方法检测IRAK1 rs3027898和rs1059703基因多态性,收集并计算RA患者临床参数:发病年龄、性别、RF抗体、抗CCP抗体、RA疾病活动(DAS28≥3.2)、骨破坏和用药情况。结果 RA组IRAK1 rs3027898和rs1059703的基因型频率和等位基因频率与健康对照组比较,差异无统计学意义(P>0.05)。RA患者IRAK1 rs3027898和rs1059703基因型与发病年龄、性别、RF抗体和抗CCP抗体阳性率、骨破坏阳性率均无相关性(P>0.05)。RA患者IRAK1 rs3027898基因型与RA疾病活动无相关性(P>0.05),RA患者IRAK1 rs1059703基因型与RA疾病活动存在相关性(P<0.05),携带CT+TT基因型RA患者疾病活动的风险是携带CC基因型RA患者4.243倍(P=0.023,OR=4.243,95%CI为1.223～14.715)。结论我国汉族人群中,IRAK1 rs3027898和rs1059703多态性与RA的易感性无关,但IRAK1 rs1059703多态性可能是RA患者疾病活动的一个遗传危险因素。     

Genetic polymorphisms of interleukin 17A and interleukin 17F and their association with inflammatory bowel disease in a Chinese Han population

Objective

Interleukin-17A and interleukin-17F (IL-17A and IL-17F) are candidate genes for chronic inflammatory disease. We investigated the association between IL17A/F gene polymorphisms and susceptibility to and clinical features of inflammatory bowel disease (IBD).

Methods

A total of 270 ulcerative colitis (UC) patients, 82 Crohn’s disease (CD) patients and 268 healthy controls were recruited in this study. Genomic DNA was extracted and analyzed for IL17A/F gene polymorphisms using ligase detection reaction allelic technology.

Results

Compared to the controls, the mutant allele C for IL17F rs763780 was significantly more common in CD patients [14.0 vs 8.4 %, P = 0.033, odds ratio (OR) 1.18, 95 % confidence interval (CI) 1.41–3.04] and was associated with the disease lesion location. This variant of IL17F rs763780 also had a weak correlation with the age of UC onset (P = 0.05, OR 0.97, 95 % CI 0.94–1.00). The IL17A (rs2275913, G-197A) variant had a weak association with the severity of disease: patients with the mutant allele A tended to suffer mild active UC. The haplotype (GGTT) of IL17A formed with four single nucleotide polymorphisms (rs2275913, rs8193037, rs8193038, and rs3804513) was associated with an increased risk of UC (P = 0.034, OR 4.58, 95 % CI 1.54–13.64).

Conclusions

The IL17F (rs763780, 7488T/C) variant was associated with an increased risk for the development of CD, and affected some clinical features of UC and CD. The IL17A (rs2275913, G-197A) variant had a weak association with the severity of UC. There was a risk haplotype in IL17A which could increase the risk of UC.     

Estrogen receptor alpha gene (ESR1) polymorphism and its interaction with smoking and drinking contribute to susceptibility of systemic lupus erythematosus

The aim of this study is to investigate the association of estrogen receptor alpha gene (ESR1) polymorphisms, additional gene–gene, and gene–environment interaction with systemic lupus erythematosus (SLE) risk. SNPStats (available online at http://bioinfo.iconcologia.net/SNPstats) was used to investigate the Hardy–Weinberg equilibrium (HWE) in controls and association between SNP and SLE risk. Generalized multifactor dimensionality reduction (GMDR) was used to screen the interactions among SNPs and environmental risk factors; SLE risk was significantly higher in carriers of rs2234693 C allele than those with TT (TC + CC versus TT), adjusted OR (95%CI) = 1.57 (1.21–2.06), and was also higher in carriers of rs9340799 G allele than those with AA (AG + GG versus AA), adjusted OR (95%CI) = 1.68 (1.24–2.13). However, we also find no association between rs2228480 and SLE risk after covariates adjustment. We found a significant two-locus model (p = 0.0010) involving rs2234693 and smoking; the cross-validation consistency of this model was 10/10, and the testing accuracy was 62.70%. Smokers with TC or CC of rs2234693 genotype have the highest SLE risk, compared to never-smokers with TT of rs2234693 genotype, OR (95%CI) was 2.50 (1.65–3.42), after covariates adjustment for gender, age, alcohol drinking, and BMI. We found that C allele of rs2234693 and G allele of rs9340799 within ESR1 gene, their interaction between rs2234693 and current smoking were all associated with increased SLE risk.     

Lack of association between IL-23R gene polymorphisms and systemic lupus erythematosus in a Chinese population

Objective

The aim to this study was to investigate the association between the single-nucleotide polymorphisms (SNPs) of interleukin (IL)-23 receptor gene and systemic lupus erythematosus (SLE) in a Chinese population.

Methods

A case–control study was performed to investigate the associations of SNPs in IL-23R gene (rs10889677 and rs1884444) with susceptibility to SLE in 521 Chinese SLE patients and 527 normal controls. The chi-square test and unconditional Logistic regression were used to analysis by SPSS 10.1 software.

Results

No significant differences were detected for the distribution of allele and genotype frequencies of these two SNPs between patients and controls as well as SLE patients with nephritis (LN) and those without nephritis.

Conclusion

The findings suggest that the polymorphisms of IL-23R gene might not contribute to the susceptibility of SLE in the Chinese population.     

Associations of VCAM-1 gene polymorphisms with obesity and inflammation markers

Objective

Among the inflammatory mediators involved in the pathogenesis of obesity, cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) stand out. The aim of this study was to investigate the associations of ICAM-1 and VCAM-1 gene variants with obesity and to investigate the associations between these genetic polymorphisms and CRP, UA, and WBC count.

Method

Four SNPs of the VCAM-1 gene (rs3176860, rs2392221, rs3917010 and rs3176879) and two SNPs of the ICAM-1 gene (rs281432 and rs5498) were analyzed in 181 control (18 < BMI < 23) and 144 obese (BMI ≥ 25) subjects. The SNPs were genotyped by direct sequencing.

Results

In allele frequency analysis, the G allelic frequency of rs3176860 in the VCAM-1 gene was lower in the obese group (30.9%) than in the controls (41.2%) (P = 0.007). The C allelic frequency of rs3917010 was lower in the obese group (18.1%) than in the control (25.1%) (P = 0.03). In the haplotype analysis of VCAM-1 gene, the ht1 (ACA) was higher and ht2 (GCC) was lower in the obese subjects than in the controls (P = 0.0057 and P = 0.037, respectively). In the obese group, participants carrying the G allele of rs3176860 of the VCAM-1 gene showed a higher percentage of segmented neutrophils and CRP levels than those carrying only the A allele (P = 0.028 and P = 0.042, respectively).

Conclusions

The results of this study suggest that VCAM-1 gene variants may be related to obesity and inflammatory markers in the Korean population.

     

A Systematic Review and Meta-Analysis on Self-Management for Improving Risk Factor Control in Stroke Patients

Purpose

The aims of this review were to describe the self-management interventions used to improve risk factor control in stroke patients and quantitatively assess their effects on the following: 1) overall risk factor control from lifestyle behaviour (i.e. physical activity, diet and nutrition, stress management, smoking, alcohol, and medication adherence), and medical risk factors (i.e. blood pressure, cholesterol, blood glucose) and (2) individual risk factors.

Method

We systematically searched the PubMed, PsycINFO, CINAHL and Cochrane Database of Systematic Reviews databases to September 2015 to identify relevant randomized controlled trials investigating self-management to improve stroke risk factors. The self-management interventions were qualitatively described, and the data included in meta-analyses.

Results

Fourteen studies were included for review. The model estimating an effect averaged across all stroke risk factors was not significant, but became significant when four low-quality studies were removed (SMD = 0.10 [95 % CI = 0.02 to 0.17], I ² = 0 %, p = 0.01). Subgroup analyses revealed a significant effect of self-management interventions on lifestyle behaviour risk factors (SMD = 0.15 [95 % CI = 0.04 to 0.25], I ² = 0 %, p = 0.007) but not medical risk factors. Medication adherence was the only individual risk factor that self-management interventions significantly improved (SMD = 0.31 [95 % CI = 0.07 to 0.56], I ² = 0 %, p = 0.01).

Conclusion

Self-management interventions appear to be effective at improving overall risk factor control; however, more high-quality research is needed to corroborate this observation. Self-management has a greater effect on lifestyle behaviour risk factors than medical risk factors, with the largest effect at improving medication adherence.

     

Chronic hepatitis C viral infection among SLE patients: the significance of coexistence

The association between viral infection and autoimmune diseases is an established phenomenon in medicine. Hepatitis C viral infection is known to have such an association; however, its association with systemic lupus erythematosus has not been studied in a real life study driven from a large national database. The objective of this study was to investigate the association between SLE and chronic hepatitis C viral infection. Patients with SLE were compared with age- and sex-matched controls regarding the proportion chronic HCV infection. Chi-square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services in Israel. There was a significant higher proportion of hepatitis C viral infection in SLE patients as compared to controls (1.06 and 0.39%, respectively; p < 0.001). A significant association was also observed among patients of higher socioeconomic status. In a multivariate logistic regression analysis, SLE was significantly associated with hepatitis C viral infection (OR = 2.07, 95% CI = 1.46–2.90). To conclude, Patients with SLE have a greater proportion of chronic HCV infection than matched controls.

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Angiotensin-converting enzyme gene and endothelial nitric oxide synthase gene polymorphisms in Behçet’s disease with or without ocular involvement

Purpose

The association of known ACE gene and eNOS gene polymorphisms with BD in a group of Turkish patients with or without ocular involvement has been investigated.

Methods

The ACE and eNOS gene polymorphisms were investigated in 73 BD patients and 90 controls.

Results

The distrubition of “DD”, “ID” and “II” genotypes of the ACE gene were 32 (43.8%), 29 (39.8%) and 12 (16.4%) for BD patients and 32 (35.5%), 35 (38.9%) and 23 (25.6%) for healthy controls. There was no significant difference between the groups (p = 0.140, OR 1.44, CI 0.90–2.30). When Behçet patients with ocular involvement were compared to the control group, statistical significance was found (p = 0.049, OR 2.18, CI 1.00–4.81). The “bb”, “ba”, and “aa” genotype frequencies of the eNOS gene were 48 (65.8%), 23 (31.5%), and 2 (2.7%) for patients with BD and 75 (83.3%), 15 (16.7%), and 0 (0%) for healthy controls, respectively. The significant difference found in allelic frequencies between the two groups (p = 0.011, OR 2.32, CI 1.11–4.87). When Behçet patients with ocular involvement were compared, sharper statistical significance was found (p = 0.001,OR 4.61,CI 1.85–11.52).

Discussion

The ACE gene polymorphism does not play a role in the pathogenesis of BD. The findings of the eNOS gene polymorphisms confirmed the significant association with BD and even more in patients with ocular involvement.     

Prognostic and clinicopathological significance of PD-L1 in patients with renal cell carcinoma: a meta-analysis based on 1863 individuals

The prognostic significance of PD-L1 in renal cell carcinoma (RCC) had been investigated in previous studies; however, the results remain controversial. The primary aim of this meta-analysis was to investigate the prognostic and clinicopathological significance of the PD-L1 expression in patients with RCC. Relevant literature was identified form PubMed, Embase, Web of Science and Cochrane library, which compared the prognostic significance between PD-L1 expression and RCC. Hazard ratios (HRs) for survival outcomes and odds ratios (ORs) for clinical parameters associated with PD-L1 were extracted from eligible studies. Heterogeneity was assessed using the I² value. The fixed-effects model was used if there was no evidence of heterogeneity; otherwise, the random-effects model was used. Publication bias was evaluated using Begg’s funnel plots and Egger’s regression test. A total of 1863 patients from ten eligible studies were analyzed. The results showed that PD-L1 expression is associated with poor overall survival in clear cell RCC (ccRCC) (HR = 2.76, 95%CI: 2.25–3.38, I² = 14.4%, P < 0.001) and non-clear cell RCC (non-ccRCC) (HR = 2.77, 95%CI: 1.62–4.72, I² = 28.8%, P < 0.001). In addition, PD-L1 expression was found to be significantly associated with primary tumor stage (OR = 1.76, 95%CI: 1.39–2.23; I² = 56.3%), regional lymph node involvement (OR = 2.10, 95%CI: 1.48–2.98; I² = 14.9%), distant metastases (OR = 2.69, 95%CI: 2.05–3.54; I² = 0.0%), nuclear grade (OR = 1.72, 95%CI: 1.32–2.23; I² = 79.4%) and histologic tumor necrosis (OR = 2.25, 95%CI: 1.59–3.18; I² = 66.1%) in patients with RCC. The outcome stability was confirmed by sensitivity analysis. Both the Begg’s funnel plot test (P = 0.276) and the Egger’s (P = 0.388) verified that there was no publication bias within the included studies. This study suggests that PD-L1 expression is correlated with poor prognosis and advanced clinicopathological features in RCC patients.     

Associations between PXK and TYK2 polymorphisms and systemic lupus erythematosus: a meta-analysis

Objective

The aim of this study was to determine whether phox homology domain containing serine/threonine kinase (PXK) and tyrosine kinase 2 (TYK2) confer susceptibility to systemic lupus erythematosus (SLE).

Materials and methods

The authors conducted meta-analyses on associations between SLE susceptibility and the rs6445975 polymorphism of PXK and the rs2304256, rs12720270, rs280519, and rs1272036 polymorphisms of TYK2.

Results

A total of 13 separate comparisons studies were included in this meta-analysis. Meta-analysis identified an association between SLE and the 2 allele of the rs6445975 polymorphism in the overall population [odds ratio (OR)?=?1.151, 95?% confidence interval (CI)?=?1.086–1.291, P?=?1.8E?06]. Stratification by ethnicity identified a significant association between this polymorphism and SLE in Europeans (OR?=?1.198, 95?% CI?=?1.118–1.285, P?=?3.4E?07), but not in Asians. Meta-analysis identified a significant negative association between SLE and the 2 allele of the rs2304256 polymorphism in the overall population (OR?=?0.808, 95?% CI?=?0.659–0.990, P?=?0.040), and a significant negative association was found in Europeans, but not in Asians.

Conclusions

This meta-analysis shows that the rs6445975 polymorphism of PXK and the rs2304256 polymorphism of TYK2 are associated with the development of SLE in Europeans.