Association between <Emphasis Type="Italic">IL17A</Emphasis> and <Emphasis Type="Italic">IL17F</Emphasis> polymorphisms and risk of Henoch–Schonlein purpura in Chinese children

Previous studies suggested that interleukin-17 and Th17 cell play an important role in the pathogenesis of childhood Henoch–Schonlein purpura (HSP). The purpose of our study is to elucidate whether the IL17A and IL17F gene polymorphisms are susceptibility genes for the development of HSP in Chinese children. A total of 148 HSP patients and 202 controls were enrolled for analyzing the single nucleotide polymorphisms (SNP) of IL17A (rs2275913, rs8193037 and rs3819025) and IL17F (rs763780 and rs9463772). TaqMan Real-Time polymerase chain reaction method was used in SNP genotyping. Compared to the healthy controls, the IL17A rs2275913 variant allele A showed a significant association with HSP [odds ratio (OR) 0.70; 95 % CI 0.51–0.94, P = 0.018]. Genotyping analysis demonstrated rs2275913 was associated with a decreased HSP risk (G/A vs. G/G: OR 0.56; 95 % CI 0.33–0.95; A/A vs. G/G: OR 0.46; 95 % CI 0.24–0.86; P = 0.032). Also, our findings showed that the A allele of IL17A rs3819025 was associated with a higher risk of HSP nephritis (OR 1.61; 95 % CI 1.00–2.58; P = 0.047). In addition, a risk haplotype of IL17A (GGA) was found (OR 1.84; 95 % CI 1.17–2.88; P = 0.008). However, no significant differences between HSP patients and healthy controls were observed when comparing genotype, allele or haplotype frequencies of the IL17F rs763780 and rs9463772 polymorphisms. In this study, we confirmed that the rs2275913 polymorphism of the IL17A gene was associated with susceptibility to HSP in Chinese children. However, there was no relationship between IL17F rs763780 and rs9463772 polymorphisms and HSP susceptibility.     

Genetic polymorphisms of dsRNA ligating pattern recognition receptors TLR3, MDA5, and RIG-I. Association with systemic lupus erythematosus and clinical phenotypes

This study aimed to demonstrate possible associations between genetic polymorphisms in Toll-like receptor 3, interferon induced with helicase C domain 1 (IFIH1) and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 and systemic lupus erythematosus (SLE), including the phenotypes lupus nephritis and malar rash, as well as the presence of autoantibodies against nucleic acid-containing complexes. Genotyping was carried out in two Danish cohorts [Copenhagen (CPH) and Odense (ODE)] totaling 344 patients and was compared with 641 previously genotyped healthy controls. In the ODE cohort, the patients were only genotyped for the rs1990760 polymorphism of IFIH1. Single nucleotide polymorphisms (SNPs) were determined by a multiplex bead-based assay (CPH cohort) or real-time PCR (ODE cohort). Associations were investigated using the Cochran–Armitage trend test. The odds ratio (OR) for minor allele homozygotes versus major allele homozygotes suggested a protective effect of the IFIH1 rs1990760 SNP for SLE in the ODE cohort [OR 0.52, 95 % confidence intervals (95 % CI) 0.31–0.88, Pcorr. = 0.05] but not in the CPH cohort, although the OR suggested a trend in the same direction, and when combining the two patient cohorts, ORs were 0.57, 95 % CI 0.37–0.88. None of the other investigated polymorphisms showed any association with SLE. Regarding phenotypes, we found a statistically significant association between rs1990760 and malar rash in the CPH cohort, with ORs suggesting a protective effect (OR 0.28, 95 % CI 0.13–0.62 for heterozygotes and OR 0.11, 95 % CI 0.03–0.41 for homozygotes, Pcorr. = 0.0001). There were no significant associations between rs1990760 and presence of anti-dsDNA, anti-U1RNP, or anti-Smith antibodies. Our study supports previous findings of an association between the rs1990760 polymorphism of IFIH1 and SLE and indicates that this SNP may also be associated with malar rash in SLE patients although this finding needs confirmation.     

Genetic polymorphisms of OCT-1 confer susceptibility to severe progression of primary biliary cirrhosis in Japanese patients

Background

To identify the genetic factors involved in the pathogenesis of primary biliary cirrhosis (PBC), we focused on the organic cation transporter 1 (OCT1/SLC22A1), which is closely associated with phosphatidylcholine synthesis in hepatocytes.

Methods

We selected four (rs683369, rs2282143, rs622342 and rs1443844) OCT-1 single nucleotide polymorphisms (SNPs), and genotyped these SNPs using the TaqMan probe method in 275 Japanese PBC patients and 194 gender-matched, healthy volunteers as controls.

Results

The Chi-square test revealed that the rs683369 variant allele (G) was associated with insusceptibility to PBC development [P = 0.009, odds ratio (OR) 0.60, 95 % confidence interval (CI) 0.40–0.88] in an allele model, and that the rs683369 variant allele (G) was associated with jaundice-type progression in a minor allele dominant genotype model (P = 0.032, OR 3.10, 95 % CI 1.05–9.14). The OCT-1 rs2282143 variant (T) and rs622342 variant (C) were also associated with jaundice-type progression in a minor allele recessive genotype model (P = 0.0002, OR 10.58, 95 % CI 2.36–47.54, and P = 0.006, OR 7.84, 95 % CI 1.39–44.36, respectively). Furthermore, the association of OCT-1 rs683369 and rs622342 with susceptibility to jaundice-type progression was confirmed by a replication study with a distinct set of PBC patients who underwent liver transplantation.

Conclusions

The present study is the first report on the association of OCT-1 genetic polymorphisms with the overall development and jaundice-type progression of PBC.     

Genetic Variants of Peroxisome Proliferator-Activated Receptor δ Are Associated with Gastric Cancer

Background

Peroxisome proliferator-activated receptors (PPAR) are implicated in pathogenesis of insulin resistance and cancers of the digestive system.

Aim

We investigated the associations of single nucleotide polymorphisms (SNPs) of PPAR δ and γ with gastric cancer and explored interactions with risk factors of gastric cancer.

Methods

We conducted our analysis in a case–control study of 196 gastric cancer patients and 397 controls residing in the Taixing region of Jiangsu, China. Six SNPs in the PPARδ (rs2076167, rs3734254) and PPARγ genes (rs10865710, rs1801282, rs3856806, rs13306747) were genotyped. We employed logistic regression to evaluate the association between each genotype and gastric cancer and tested for gene–environment interaction with Helicobacter pylori (H. pylori) infection, smoking status, and meat and salt intake.

Results

We found that the G/G variant rs2076167, in tight linkage disequilibrium with rs3734254 (R ² = 0.97), was associated with increased risk of gastric cancer in a recessive model (OR 2.20, 95 % CI 1.12, 4.32). The association between G/G variant of rs2016167 and gastric cancer was particularly strong among those with higher salt intake (OR 5.11, 95 % CI 1.11, 23.5), but did not vary by H. pylori infection or smoking status.

Conclusion

We found that genetic variants of PPARδ were associated with gastric cancer. If the association is confirmed in larger studies, it may implicate a role for PPARδ activators, such as insulin-sensitizing agents, in prevention of gastric cancer.     

Association between NINJ2 gene polymorphisms and ischemic stroke: a family-based case–control study

Novel susceptibility genes related to ischemic stroke (IS) are proposed in recent literatures. Population-based replicate studies would cause false positive results due to population stratification. 229 recruit IS patients and their 229 non-IS siblings were used in this study to avoid population stratification. The family-based study was conducted in Beijing from June 2005 to June 2012. Association between SNPs and IS was found in the sibship discordant tests, and the conditional logistic regression was performed to identify effect size and explore gene–environment interactions. Significant allelic association was identified between NINJ2 gene rs11833579 (P = 0.008), protein kinase C η gene rs2230501 (P = 0.039) and IS. The AA genotype of rs11833579 increased 1.51-fold risk (95 % CI 1.04–3.46; P = 0.043) of IS, and it conferred susceptibility to IS only in a dominant model (OR 2.69; 95 % CI 1.06–6.78; P = 0.036]. Risk of IS was higher (HR 3.58; 95 % CI 1.54–8.31; P = 0.003) especially when the carriers of rs11833579 AA genotype were smokers. The present study suggests A allele of rs11833579 may play a role in mediating susceptibility to IS and it may increase the risk of IS together with smoking.     

Association of glucokinase regulatory gene polymorphisms with risk and severity of non-alcoholic fatty liver disease: an interaction study with adiponutrin gene

Background

Recent genome-wide association studies demonstrated an association between single nucleotide polymorphisms (SNPs) on the glucokinase regulatory gene (GCKR) with hepatic steatosis. This study attempted to investigate the association of GCKR rs780094 and rs1260326 with susceptibility to non-alcoholic fatty liver disease (NAFLD) and its severity.

Methods

The genotypes were assessed on 144 histologically confirmed NAFLD patients and 198 controls using a Sequenom MassARRAY platform.

Results

The GCKR rs1260326 and rs780094 allele T were associated with susceptibility to NAFLD (OR 1.49, 95 % CI 1.09–2.05, p = 0.012; and OR 1.51, 95 % CI 1.09–2.09, p = 0.013, respectively), non-alcoholic steatohepatitis (NASH) (OR 1.55, 95 % CI 1.10–2.17, p = 0.013; and OR 1.56, 95 % CI 1.10–2.20, p = 0.012, respectively) and NASH with significant fibrosis (OR 1.50, 95 % CI 1.01–2.21, p = 0.044; and OR 1.52, 95 % CI 1.03–2.26, p = 0.038, respectively). Following stratification by ethnicity, significant association was seen in Indian patients between the two SNPs and susceptibility to NAFLD (OR 2.64, 95 % CI 1.28–5.43, p = 0.009; and OR 4.35, 95 % CI 1.93–9.81, p < 0.0001, respectively). The joint effect of GCKR with adiponutrin rs738409 indicated greatly increased the risk of NAFLD (OR 4.14, 95 % CI 1.41–12.18, p = 0.010). Histological data showed significant association of GCKR rs1260326 with high steatosis grade (OR 1.76, 95 % CI 1.08–2.85, p = 0.04).

Conclusion

This study suggests that risk allele T of the GCKR rs780094 and rs1260326 is associated with predisposition to NAFLD and NASH with significant fibrosis. The GCKR and PNPLA3 genes interact to result in increased susceptibility to NAFLD.     

Interferon regulatory factor 5 polymorphisms in sarcoidosis

Objective

Interferon regulatory factor 5 (IRF5) gene polymorphisms are associated with susceptibility to autoimmune diseases. The aim of this study is to determine the roles of IRF5 single-nucleotide polymorphisms (SNPs) in sarcoidosis.

Methods

A total of 175 Japanese patients with biopsy-proven sarcoidosis and 150 sex-matched controls were genotyped for four IRF5 SNPs: rs729302A/C, rs2004640G/T, rs10954213A/G, and rs2280714G/A. The associations of these SNPs with susceptibility to sarcoidosis were examined.

Results

Carriage of rs10954213A and rs2280714A conferred significant risks for sarcoidosis [carriage of rs10954213A: odds ratio (OR) = 1.96, 95 % confidence interval (CI) = 1.15–3.33, P = 0.01, corrected P = 0.04; carriage of rs2280714A: OR = 1.97, 95 % CI = 1.22–3.16, P = 0.005, corrected P = 0.02]. The haplotype carrying rs10954213A and rs2280714A (haplotype 2) was significantly associated with susceptibility to sarcoidosis (OR = 2.00, 95 % CI = 1.24–3.24, P = 0.004, corrected P = 0.01). rs729302 and rs2004640 were not associated with susceptibility to sarcoidosis, whereas carriage of rs2004640G was protective against pulmonary hypertension (OR = 0.017, 95 % CI = 0.002–0.15, P < 0.001, corrected P < 0.001).

Conclusion

A haplotype carrying two functional SNPs of IRF5, rs10954213A and rs2280714A, was associated with the risk of sarcoidosis in the Japanese population.     

Genetic markers of bevacizumab-induced hypertension

Purpose

There are currently no validated biomarkers predicting bevacizumab treatment outcome or toxicity. We combined biomarker data from six phase III trials of bevacizumab to assess whether genetic variation in vascular endothelial growth factor-A (VEGF-A) pathway or hypertension-related genes are associated with bevacizumab-induced hypertension.

Experimental design

Germline DNA was available from 1,631 patients receiving bevacizumab-containing therapy for advanced solid tumors. Overall, 194 white patients had grade 1–4 bevacizumab-induced hypertension. In total, 236 single nucleotide polymorphisms (SNPs) located in VEGF-A, VEGF-A receptors (FLT1 and KDR), and other genes were selected using a SNP tagging approach and genotyped. A logistic regression on individual patient data was performed after adjustment for cancer type and five other covariates.

Results

Ten SNPs were associated with bevacizumab-induced hypertension (P ≤ 0.05), but none surpassed the threshold adjusted for multiple testing (P < 0.0002). The most significant VEGF-A pathway SNP was rs1680695 in EGLN3 [allelic odds ratio (OR) 1.50 [95 % confidence interval (Cl) 1.09–2.07], P = 0.012]. Two additional SNPs, rs4444903 in EGF and rs2305949 in KDR, were associated with hypertension (allelic OR 1.57 [95 % CI 1.17–2.11], P = 0.0025; allelic OR 0.62 [95 % CI 0.42–0.93], P = 0.020, respectively) and closely linked to nearby functional variants. Consistent with previous reports, rs11064560 in WNK1 was also associated with bevacizumab-induced hypertension (OR 1.41 [95 % CI 1.04–1.92], P = 0.028).

Conclusions

The genes described in this large genetic analysis using pooled datasets warrant further functional investigation regarding their role in mediating bevacizumab-induced hypertension.     

The association between the polymorphism rs2231142 in the ABCG2 gene and gout risk: a meta-analysis

Gout is a common metabolic disorder with high heritability. We tried to explore the association between rs2231142 and gout. We searched “rs2231142 or Q141K and gout” in four databases and scholar searching website until 1 June, 2013 and included data from 52,010 participants in meta-analysis and subgroup analysis. The T allele of rs2231142 was associated with increased gout susceptibility (odds ratio [OR] [95 % confidence interval (95 % CI)]?=?1.73 [1.55–1.91], P?P?P?P?Pacific Islanders with OR (95 % CI)?=?2.94 (1.72–4.15), P?P?=?0.061. No publish or other biases were observed. The T allele of rs2231142 was associated with increased risk of gout.     

TLR9 polymorphisms and systemic lupus erythematosus risk: an update meta-analysis study

It has been reported that the Toll-like receptor 9 (TLR9) gene polymorphisms may be associated with systemic lupus erythematosus (SLE) risk. However, some studies yielded conflicting results. Therefore, a comprehensive meta-analysis was performed to assess the precise association between TLR9 polymorphisms and SLE susceptibility. We performed a systematic search in PubMed, Embase (Ovid), China National Knowledge Internet, and Wanfang databases up to July 15, 2015. Odds ratio (OR) and 95 % confidence interval (CI) were used to pool the effect size. Statistical analyses were performed with STATA 11.0 software. In total, 21 studies from nineteen articles with 10,273 subjects were included in this meta-analysis. The overall results suggested that there was a statistically significant association between TLR9 rs187084 polymorphism and SLE risk observed in recessive model (TT vs. TC + CC: OR 1.17, 95 % CI 1.05–1.30, P = 0.005), codominant model (TT vs. CC: OR 1.22, 95 % CI 1.03–1.43, P = 0.019), and allele model (T vs. C: OR 1.15, 95 % CI 1.02–1.30, P = 0.020) in Asians. However, we found that there may be no significant association between the other three TLR9 polymorphisms and SLE risk in either Asians or non-Asians. In conclusion, the meta-analysis results suggested that TLR9 rs187084 polymorphism may increase the risk of SLE in Asians. However, no significant association between TLR9 SNPs (rs352139, rs352140, and rs5743836) and SLE risk was identified.     

<Emphasis Type="Italic">C-reactive protein</Emphasis> +1444CT (rs1130864) genetic polymorphism is associated with the susceptibility to systemic lupus erythematosus and C-reactive protein levels

The T rare allele of +1444CT (rs1130864) polymorphism of C-reactive protein (CRP) has been associated with increased CRP levels in some inflammatory conditions, but its role on systemic lupus erythematosus (SLE) susceptibility and on CRP levels in SLE patients remains uncertain. The objective of the study was to evaluate the association between the rs1130864 CRP polymorphism with SLE susceptibility, disease activity, and CRP levels in SLE Brazilian patients. The study enrolled 176 SLE patients and 137 controls. SLE disease activity was assessed using the SLE Disease Activity Index (SLEDAI). The rs1130864 CRP polymorphism was determined using polymerase chain reaction and restriction fragment length polymorphism. SLE patients presented higher body mass index (p = 0.046) and CRP levels (p = 0.017) than controls. The genotype and allele frequencies of patients differed from controls [CC vs. CT = odds ratio (OR) 1.730, 95% confidence interval (CI) 1.068–2.803, p = 0.035; CC vs. TT = OR 3.667, 95% CI 1.410–9.533, p = 0.009; C vs. T = OR 1.883, 95% CI 1.299–2.728, p = 0.001)]. Patients carrying the T allele presented higher CRP levels (p = 0.009), were more frequent Caucasians (p = 0.018), and with no use of immunosuppressive treatment (p = 0.004) than those carrying the C allele. However, the SLEDAI and anti-double-stranded DNA positivity did not differ from those carrying T vs. C allele (p = 0.595 and p = 0.243, respectively). The rs1130864 CRP polymorphism was associated with SLE susceptibility and CRP levels, but not with disease activity, suggesting that this polymorphism may play a role in the pathophysiology of SLE through increasing the CRP that, probably, plays an inflammatory role in SLE pathophysiology.     

Single nucleotide polymorphisms of CD244 gene predispose to renal and neuropsychiatric manifestations with systemic lupus erythematosus

The objective of this study was to explore the association of single nucleotide polymorphisms (SNPs) of the CD244 gene with several clinical features of systemic lupus erythematosus (SLE). Two hundred and forty-three patients with SLE and 369 healthy controls were enrolled. Two SNPs (rs6682654 and rs3766379) in the CD244 gene were determined by allelic discrimination using a specific TaqMan probe. Only SNP rs3766379 was significantly associated with susceptibility to SLE [P = 0.009; odds ratio (OR) 1.28; 95% confidence interval (CI) 1.04–1.57]. The association was preferentially observed in subsets of SLE patients with nephritis and neuropsychiatric lupus. The frequency of the rs6682654 C allele was strongly associated with nephritis and neuropsychiatric lupus (P = 0.00065; OR 1.99; 95% CI 1.34–2.95, and P = 1.6 × 10^?7; OR 3.47; 95% CI 2.12–5.70, respectively), as was the frequency of the rs3766379 T allele (P = 0.0014; OR 1.86; 95% CI 1.27–2.71, and P = 2.6 × 10^?7; OR 3.15; 95% CI 2.00–4.96, respectively). In this study, an SNP of the CD244 gene was associated with susceptibility to SLE. There was a strikingly strong association in SLE patients with nephritis and neuropsychiatric lupus, suggesting that this genetic marker could predict involvement of those severe complications.     

Monocyte subsets and monocyte-platelet aggregates in patients with unstable angina

Monocyte subsets and monocyte-platelet aggregates (MPAs) play important role in atherosclerosis and thrombosis. We aimed to determine their changes in patients with unstable angina (UA). In this cross-sectional case–control study, Global Registry of Acute Coronary Events (GRACE) score was determined in 95 UA patients without elevated troponin level. Thirty age-and-sex matched stable coronary heart disease (CHD) subjects served as control group. The classical (CD14++CD16?, Mon1), the intermediate (CD14++CD16+, Mon2) and the non-classical (CD14+CD16++, Mon3) monocytes, as well as subset-specific MPAs, were measured by flow cytometry. Compared with stable CHD patients, UA patients had increased Mon2 and Mon3 counts (all P < 0.001). For UA subjects, compared with GRACE score-determined low risk patients (GRACE score ≤108, n = 70), intermediate-to-high risk patients (GRACE score >108, n = 25) had higher counts of Mon2 and total MPAs, as well as Mon1- and Mon2-associated MPAs (all P < 0.001). Adjusted binary logistic regression analysis revealed that increased counts of Mon2 subset (for per 5 cells/μL increase, OR 1.186, 95 % CI 1.044–1.347, P = 0.009), Mon2 MPAs (for per 5 cells/μL increase, OR 1.228, 95 % CI 1.062–1.421, P = 0.006) and total MPAs (for per 5 cells/μL increase, OR 1.072, 95 % CI 1.010–1.137, P = 0.022) independently associated with GRACE score-determined intermediate-to-high risk UA patients. In UA patients with intermediate-to-high risk (determined by GRACE score), counts of Mon2 subset, Mon2-associated MPAs and total MPAs are increased, which are independent of traditional risk factors.     

Associations between PTPRC rs10919563 A/G and FCGR2A R131H polymorphisms and responsiveness to TNF blockers in rheumatoid arthritis: a meta-analysis

We aimed to investigate whether the PTPRC rs10919563 A/G and Fc gamma receptor 2A (FCGR2A) R131H polymorphisms can predict the response to anti-TNF therapy in rheumatoid arthritis (RA) patients. We conducted a meta-analysis of studies on the association between the PTPRC rs10919563 A/G or the FCGR2A R131H polymorphism and responsiveness to anti-TNF therapy in RA patients. Eighteen studies (twelve on PTPRC and six on FCGR2A) from eight articles involving 3058 patients were considered in this meta-analysis. The meta-analysis showed a significant association between the PTPRC rs10919563 A allele and response to TNF-α blockers in RA. The OR of the PTPRC A allele was significantly lower in responders (OR = 0.584, 95 % CI = 0.409–0.835, P = 0.003). Meta-analysis revealed no association between the FCGR2A HH + HR genotype and responsiveness to TNF blockers in all study subjects (OR = 0.762, 95 % CI = 0.543–1.068, P = 0.115). However, stratification by TNF inhibitor type showed that the FCGR2A HH + HR genotype was associated with responsiveness to adalimumab (OR = 0.591, 95 % CI = 0.369–0.947, P = 0.029), but not infliximab and etanercept (OR = 0.929, 95 % CI = 0.354–2.440, P = 0.881; OR = 0.804, 95 % CI = 0.293–2.207, P = 0.673). The PTPRC rs10919563 A allele shows a poor response to anti-TNF therapy, and the FCGR2A HH + HR genotype shows a poor response to adalimumab for RA. Genotyping for these polymorphisms may be useful for predicting the response to TNF-α blockers with respect to personalized medicine.     

Association of Kir6.2 gene rs5219 variation with type 2 diabetes: A meta-analysis of 21,464 individuals

Aims

rs5219 is in Potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) E23K gene, located at 11p15.1. Researches on the association between rs5219 gene polymorphism with type 2 diabetes mellitus (T2DM) were performed extensively, but the results remain controversial. To investigate the relationship, a meta-analysis involving 21,464 individuals was conducted.

Acid Suppression Therapy as a Risk Factor for Candida Esophagitis

Background/Aim

As the prevalence of reflux esophagitis increases, so does the use of gastric acid suppressants. This study aimed to document the prevalence of Candida esophagitis (CE) at a single Korean university hospital over the last 5 years and to evaluate its risk factors.

Methods

To investigate the prevalence of CE, we conducted a retrospective analysis of 55,314 individuals who underwent a screening esophagogastroduodenoscopy as part of a health check-up between January 2006 and December 2010 at Kyung Hee University Hospital in Seoul, Korea. A total of 250 patients who were treated for CE between January 2008 and August 2011 and 500 age- and sex-matched non-CE patients were enrolled in this study. The rates of recent gastric acid suppression therapy and other well-known risk factors in the two groups were compared.

Results

The prevalence of CE was 0.35 % and increased each year (linear-by-linear association, P = 0.001). Univariate analysis showed that gastric acid suppression therapy, malignancy, DM and steroid therapy were related to CE. Multivariate analysis also showed that gastric acid suppression therapy (OR 5.11, 95 % CI 2.92–8.93 and P < 0.001), malignancy (OR 18.68, 95 % CI 6.37–54.75 and P < 0.001), DM (OR 2.67, 95 % CI 1.70–4.21 and P < 0.001) and steroids therapy (OR 6.74, 95 % CI 1.37–33.05 and P = 0.019) were related to CE.

Conclusions

The prevalence of CE in Korea is increasing. Also, our results indicate that acid suppression therapy is a meaningful risk factor for CE.     

Sorafenib enhances effects of transarterial chemoembolization for hepatocellular carcinoma: a systematic review and meta-analysis

Background and aim

Combination therapy of sorafenib and transarterial chemoembolization (TACE) showed benefits for hepatocellular carcinoma (HCC). This systematic review aims for evaluation of efficacy and safety between sorafenib plus TACE and TACE alone for HCC.

Methods

We systematically searched multi-databases to identify eligible studies. Studies comparing sorafenib combined with TACE and TACE alone for HCC were included.

Results

Nine studies with 900 patients (sorafenib + TACE = 446, TACE = 454) were finally included. Sorafenib combined with TACE significantly reduced 6-month mortality [OR 0.24, 95 % confidential interval (CI) 0.09–0.68, P = 0.007] and 1-year mortality (OR 0.35, 95 % CI 0.21–0.56, P < 0.0001), but did not decrease 2-year mortality (OR 0.58, 95 % CI 0.14–2.46, P = 0.46). Although combination therapy tend to reduce 3-month (OR 0.76, 95 % CI 0.52–1.10, P = 0.15) and 6-month progression free rate (OR 0.27, 95 % CI 0.07–1.05, P = 0.06), the changes were not significant. Additionally, objective response ratio (OR 0.39, 95 % CI 0.19–0.78, P = 0.008) and clinical benefit ratio (OR 0.27, 95 % CI 0.15–0.50, P < 0.0001) also favored for combination therapy, which, however, caused higher morbidity, especially hand-foot skin reaction (OR 53.71, 95 % CI 28.86–99.93, P < 0.00001), hematological events (OR 14.8, 95 % CI 6.07–36.07, P < 0.00001), diarrhea (OR 6.62, 95 % CI 3.82–11.45, P < 0.00001), hypertension (OR 5.03, 95 % CI 3.02–8.38, P < 0.00001), rash/desquamation (OR 5.67, 95 % CI 3.58–8.99, P < 0.00001), and fatigue (OR 2.5, 95 % CI 1.09–5.72, P = 0.03).

Conclusion

Combination of sorafenib and TACE showed survival and clinical benefits in patients with HCC, though enhanced morbidity.     

C-reactive protein (CRP) polymorphisms and haplotypes are associated with SLE susceptibility and activity but not with serum CRP levels in Mexican population

To evaluate the association of C-reactive protein (CRP) polymorphisms with risk of development SLE in a group of Mexican individuals. Five CRP polymorphisms (rs3093059, rs3093062, rs1800947, rs1130864, and rs1205) were determined by PCR-restriction fragment length polymorphism and SNP rs3093061 by refractory mutation system PCR assay in 126 SLE patients and 131 controls. Four of the polymorphisms showed differences between patients and controls. rs3093061 polymorphism was associated with a lower risk of developing lupus principally in the codominant 2 (OR?=?0.219, 95% CI 0.108–0.785, P =?0.015) model. rs1130864 was associated with decreased risk mainly under codominant 1 (OR?=?0.288, 95% CI 0.143–0.581, P =?0.001) model. rs1205 was associated under the over-dominant model (OR?=?0.504, 95% CI 0.270–0.942, P =?0.032). The rs3091244 polymorphism was associated with decreased risk of SLE mostly under additive (OR?=?0.605, 95% CI 0.393–0.931. P =?0.022) model. Our study establishes that rs3093061, rs1130864, rs1205, and rs3091244 polymorphisms are associated with decreased risk of developing SLE.     

Association between promoters polymorphisms of matrix metalloproteinases and risk of digestive cancers: a meta-analysis

Purpose

A variety of studies have been performed to elucidate the polymorphisms in promoter regions of matrix metalloproteinases (MMPs) associated with the risk of digestive cancers, and yet, results remain conflicting and heterogeneous. Thus, we undertook a systematic meta-analysis to determine the genetic susceptibility of MMPs to digestive cancers.

Methods

A computerized literature search was conducted in databases of PubMed, Embase, and ISI Web of Knowledge till October 2012 for any MMP genetic association study in oral squamous, gastric, esophageal, and colorectal carcinomas. Odds ratios (OR) and 95 % confidence interval (CI) were estimated for each gene under dominant and recessive models, and the heterogeneity between studies was assessed using Q test and I ² value. Overall and subgroup analysis according to anatomical sites and ethnicity was carried out. Statistical analysis was performed with Review Manager 5.0.

Results

A total of 40 eligible publications with 68 comparisons were included in this study. For MMP1 nt-1607, individuals with 2G state could increase risk of digestive cancers in total analysis (dominant: OR = 1.31, 95 % CI = 1.16–1.48, P < 0.00001; recessive: OR = 1.29, 95 % CI = 1.11–1.50, P = 0.0009). In the subgroup of tumor sites, significant associations were also observed in esophageal cancer and colorectal cancer under both genetic models. For MMP2 nt-1306, CT or TT carriers performed significant protection against digestive cancer in the dominant model (OR = 0.69, 95 % CI = 0.55–0.85, P = 0.0007) of the overall. In the subgroup analysis, significant association was found in esophageal cancer, with borderline effects in gastric cancer and oral squamous cell carcinoma. For MMP7 ?181 A/G, significant association was observed under two genetic models in the overall (dominant: OR = 1.26, 95 % CI = 1.10–1.43, P = 0.0009; recessive: OR = 1.33, 95 % CI = 1.11–1.60, P = 0.002) and in the individual cancer subgroup of esophageal cancer and gastric cancer. For MMP9 ?1,562 C/T, a borderline effect was found with digestive cancers in the total and stratified analysis of the colorectal cancer under dominant model. No association was observed in either the overall or subgroup analysis for MMP3 ?1,171 5A/6A.

Conclusions

Our meta-analysis demonstrated the fact that polymorphisms in promoter regions of MMP genes might be related to the susceptibility of digestive cancers, with cancer development for MMP1 and MMP7, and a protection against cancer for MMP2 and MMP9. Further evidences with adequate sample sizes need to be conducted.