Associations analysis of GSTM1, T1 and P1 Ile105Val polymorphisms with carpal tunnel syndrome

Oxidative stress was related with carpal tunnel syndrome (CTS). We aimed to clarify the associations between glutathione S-transferase (GST)M1, GSTT1 and GSTP1-Ile105Val polymorphisms and CTS. One hundred-forty patients with CTS and 97 healthy controls were enrolled in this study. Tinel and Phalen signs were noted as positive or negative. Functional and clinical status of patients was evaluated by the Boston Questionnaire. The intensity of hand and/or wrist pain was evaluated on 10 cm visual analog scale (VAS). We applied the polymerase chain reaction (PCR) to determine the polymorphisms of the GSTM1 and GSTT1 and the PCR-restriction fragment length polymorphism method for detecting the GSTP1-Ile105Val polymorphism. The M1 null genotype was significantly higher in patients with CTS compared to healthy controls, and the M1 null genotype seemed to increase the risk of CTS approximately two-fold (P?=?0.011; odds ratio (OR)?=?1.98; 95 % confidence interval (CI) 1.17–3.36). The M1 null, T1 present combined genotype was significantly higher in patients with CTS compared to healthy controls (P?=?0.043); however, it seemed not to increase the risk of CTS (P?=?0.14; OR?=?0.62; 95 % CI 0.33–1.76). We found significantly higher levels of the VAS, Boston Symptom Severity Scale and Phalen sign in patients with the Ile/Val or the Val/Val genotypes compared to those in patients with the Ile/Ile genotype (P?=?0.003, 0.004 and 0.044, respectively). We proposed that genes involved in the protection from oxidative stress may influence the susceptibility, clinical and functional status of CTS. The GSTM1 null genotype may be related with the development of CTS, whereas the Val allele of GSTP1-Ile105Val polymorphism may be associated with worse functional and clinical status in CTS.     

GSTT1 and GSTM1 null genotypes may facilitate hepatitis C virus infection becoming chronic

Oxidative stress contributes to hepatitis C virus (HCV)-induced liver damage. The activity of antioxidant glutathione S-transferases (GSTs) T1 and M1 is polymorphic. The GSTT1 and GSTM1 genotypes were identified in 139 HCV-infected patients and in 329 healthy individuals. Among patients, there was an excess of GSTT1 (odds ratio [OR], 2.76 [95% confidence interval [CI], 1.77-4.30]; P<.001) and GSTM1 (OR, 1.54 [95% CI, 1.02-2.35]; P=.032) null genotypes and of double-null haplotypes (OR, 3.65 [95% CI, 1.98-6.75]; P<.001). The GSTT1 null genotype, particularly if associated with the GSTM1 null genotype, may facilitate HCV infection becoming chronic.     

GSTT1 and GSTM1 Gene Polymorphisms as Major Risk Factors for Asthma in a North Indian Population

Background

According to the National Family Health Survey, asthma is one of the leading diseases in India. In order to understand the complexity of asthma, the susceptibility genes need to be targeted for their association. Glutathione S-transferases play a major role in the detoxification of metabolites of oxidative stress resulting in inflammation and asthma. In the present study, the hypothesis that GSTT1 and GSTM1 gene polymorphisms are associated with asthma was examined.

Methods

This is the first study to investigate the role of GSTT1 and GSTM1 gene polymorphisms in asthma pathogenesis in a North Indian population. A total of 824 subjects were recruited, of which 410 were asthma patients, including 323 patients suffering from allergic rhinitis. The other 414 recruits were healthy controls from regions of North India. Multiplex PCR was used for genotyping the GSTT1 and GSTM1 gene polymorphisms.

Results

The GSTT1 null allele was more prevalent in asthma patients (40?%) than in the control subjects (13.3?%), which yielded a nearly fourfold risk towards asthma with odds ratio (OR) (95?% CI)?=?4.35 (3.04–6.24), χ²?=?75.34, and p?=?0.000. The GSTM1 polymorphism also revealed a greater prevalence of the GSTM1 null allele in asthma patients (46.6?%) than in controls (39.4?%). Statistical analysis yielded a marginal risk toward asthma with OR (95?% CI)?=?1.34 (1.01–1.79), χ²?=?4.37, and p?=?0.036.

Conclusions

Polymorphisms as a result of deletions in the GSTT1 and GSTM1 genes confer an increased risk towards asthma thereby suggesting the protective role of these functional genes in the development of the disease.     

The link between genetic polymorphism of glutathione-S-transferases, GSTM1, and GSTT1 and diffuse large B-cell lymphoma in Egypt

Background

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. A number of studies have examined the role of genetic polymorphisms in the risk of DLBCL, and several variants have been identified as potential susceptibility genes, of those glutathione-S-transferases T1 and M1 (GSTT1 and GSTM1).

Aim of the work

The aim of the current study was to investigate the influence of inherited genetic polymorphisms of GSTM1 and GSTT1 genes on the susceptibility to DLBCL in Egypt.

Methods

Genotyping of the candidate genes was performed for 71 Egyptian DLBCL patients and 100 age- and gender-matched healthy controls by multiplex polymerase chain reaction technique.

Results

The frequencies of GSTT1 null, GSTM1 null, and dual null genotypes among DLBCL patients were 47.9, 52.1, and 23.9?% respectively.

Conclusion

GSTT1 null genotype conferred almost fourfold increased risk of DLBCL (OR?=?3.9, 95?% CI?=?1.97–7.75), and the risk increased when confined to male patients (OR?=?4.4, 95?% CI?=?1.57–12.63), while GSTM1 null genotype was not associated with DLBCL risk. Further studies on the functional consequences of GSTT1 and GSTM1 genetic polymorphisms would pave the way to declare their role in the pathogenesis of DLBCL or as possible predictors for response to therapy.     

The JAK2 46/1 haplotype (GGCC) in myeloproliferative neoplasms and splanchnic vein thrombosis: a pooled analysis of 26 observational studies

Numbers of observational studies suggest that the JAK2 46/1 (GGCC) haplotype may increase the risk of myeloproliferative neoplasms (MPNs) and splanchnic vein thrombosis (SVT), but the results remain controversial. We aimed to examine the association between the JAK2 46/1 haplotype and risk of MPNs and SVT by conducting a meta-analysis. PubMed, EMBASE, Cochrane Library, CBM, and CNKI databases were searched to identify eligible studies without restrictions and by reviewing reference lists of obtained articles. Both fixed and random-effects models were used to calculate the summary risk estimates. We identified 26 observational studies of the JAK2 46/1 haplotype and risk of MPNs and SVT involving 8,561 cases and 7,434 participants. In the overall analysis, it was found that the JAK2 46/1 haplotype significantly elevated the risk of MPNs (rs10974944: C vs T: odds ratio (OR)?=?2.19, 95 % confidence interval (CI)?=?1.86–2.57, P?<?0.0001; CC vs TT: OR?=?4.63, 95 % CI?=?3.32–6.47, P?<?0.0001; CT vs TT: OR?=?2.49, 95 % CI?=?2.11–2.95, P?<?0.0001; (CC?+?CT) vs TT: OR?=?2.92, 95 % CI?=?2.51–3.39, P?<?0.0001; rs12343867: C vs T: OR?=?1.88, 95 % CI?=?1.59–2.22, P?<?0.0001; CC vs TT: OR?=?3.16, 95 %CI?=?2.14–4.65, P?<?0.0001; CT vs TT: OR?=?2.04, 95 % CI?=?1.51–2.74, P?<?0.0001; (CC?+?CT) vs TT: OR?=?2.25, 95 % CI?=?1.73–2.95, P?<?0.0001) and SVT (C vs T: OR?=?1.27, 95 % CI?=?1.06–1.52, P?=?0.011; CC vs TT: OR?=?2.33, 95 % CI?=?1.42–3.81, P?=?0.001; (CC?+?CT) vs TT: OR?=?1.25, 95 % CI?=?1.02–1.53, P?=?0.034). There was no evidence of a significant association between the rs12343867 and the risk of SVT in the genetic model (CT vs TT: OR?=?1.01, 95 % CI?=?0.80–1.29, P?=?0.906). This meta-analysis provides new evidence supporting the conclusion that the JAK2 46/1 haplotype enrichment is significantly associated with the development of MPNs and SVT in these patients.     

GSTT1及GSTM1与急性髓系白血病疗效及预后的研究

目的探讨谷胱甘肽硫转移酶(GSTs)家族中GSTT1和GSTM1基因多态性与急性髓系白血病(AML)疗效,药物不良反应与预后的关系。方法AML患者180例,用多重PCR方法检测GSTT1和GSTM1基因型,比较不同基因型患者的诱导治疗完全缓解(CR)率,药物不良反应发生率,总体生存期,无复发生存期和复发率。结果(1)GSTT1和GSTM1基因双非缺失型(double-present型)患者一疗程CR率高于GSTT1,GSTM1任一基因缺失型(null型),二者差异有统计学意义(P=0.013),GSTT1/GSTM1的null基因型患者发生不CR的危险度是double-present型患者的8.736倍(95%CI1.146~66.574)。GSTT1present型一疗程CR率高于GSTT1null型,二者比较亦有统计学意义(P=0.021,OR=2.572,95%CI1.136~5.826);(2)GSTT1和GSTM1基因型分布与诱导治疗后中性粒细胞<0.5×109/L及PLT<20×109/L持续时间差异无统计学意义,GSTM1null型患者发生AST异常的危险度是GSTM1present型的2.593倍(P=0.016,95%CI1.176~5.717);(3)double-present型总体和无复发生存期较GSTT1/GSTM1的null型患者长(平均总体生存期为68.4、38.5个月,P=0.028;平均无复发生存期为73.5、34.9个月,P=0.014),GSTT1null型患者无复发生存期短于GSTT1present型患者(平均无复发生存期为26.7、64.3个月,P=0.038),但二者总体生存期无统计学意义(P=0.653)。double-present型患者复发率显著低于GSTT1/GSTM1的null型患者(13.3%、35.6%,P=0.019)。结论GSTT1,GSTM1基因型与AML患者治疗CR率、复发率、化疗的不良反应及预后均有显著相关性,GSTT1和GSTM1基因型有助于指导AML患者个体化治疗方案的制定。     

Increased risk for acute myeloid leukaemia in individuals with glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) gene defects

OBJECTIVES: Glutathione S-transferases (GST) modulate the effects of exposure to various cytotoxic and genotoxic agents, including those associated with increased risks of the myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML) and aplastic anemia (AA). Both the GST mu 1 (GSTM1) and GST theta 1 (GSTT1) genes have a null variant allele in which the entire gene is absent. In this study, we tested whether null genotypes for the GSTM1 and GSTT1 genes altered the risks for MDS, AML and AA. METHODS: Genomic DNA from 49 MDS, 38 AML and 37 AA patients and 276 controls was analysed using the polymerase chain reaction (PCR). RESULTS: The frequencies of GSTM1 (73.6%) and GSTT1 (34.2%) null genotypes were significantly higher in AML patients than in the controls (36.9 and 18.1%, respectively). A higher frequency of the combined null genotype for both genes was also observed in patients with AML (26.3% compared with 5.0% in the controls). In contrast, no differences in the frequencies of the null genotypes were found among MDS patients, AA patients and the controls. CONCLUSION: Our observation of a 4.7-fold (95% CI: 2.1-11.0) and 2.3-fold (95% CI: 1.0-5.2) increased risk associated with the GSTM1 and GSTT1 null genotypes, respectively, and a 6.6-fold (95% CI: 2.4-7.9) increased risk associated with the combined null genotype presents preliminary evidence that the inherited absence of this carcinogen detoxification pathway may be an important determinant of AML.     

GSTT1 (rs4025935) null genotype is associated with increased risk of sickle cell disease in the populations of Tabuk—Northwestern region of Saudi Arabia

Background: Glutathione system plays an important role in the protection of cells and tissue against damage from oxidative stress. Impairment of the glutathione system due to genetic polymorphism of GST genes may increase the risk and severity of sickle cell disease (SCD). Present study was, therefore, undertaken to examine the relative impact of the genetic polymorphism of GSTT1 and GSTM1 (rs4025935 and rs71748309) on susceptibility and hematological aspects of the patients with SCD.

Methods: Present study included 100 patients with SCD and 200 healthy controls from northwestern region of Saudi Arabia. GSTM1 and GSTT1 (rs4025935 and rs71748309) genotypes were investigated by using single-tube multiplex PCR technique.

Results: It was observed that patients with SCD possessed significantly higher frequency of GSTT1 null genotype (26%) than healthy controls (15%), (P?=?0.00001). Compared to the presence of GSTT1 genotype, the OR for the GSTT1 null genotype were estimated to be 4.3 (2.17–8.64, P?=?0.00001). However, such association was not observed with respect to the presence of GSTM1 null genotype. In addition, it was observed that SCD in patients with GSTT1 genotype, the mean percentage levels for HbF and HbS were 0.48 and 35.4%, respectively; however, among SCD patients with GSTT1 null genotype, the mean percentage levels were significantly higher 1.62% (P?=?0.004) and 39.38% (P?=?0.02), respectively.

Conclusion: GSTT1 null genotype is significantly associated with increased risk of SCD among the population of northwestern region of Saudi Arabia. In addition, it may be one of the important factors responsible for hematological manifestations of SCD.     

Multilineage dysplasia is associated with a poorer prognosis in patients with de novo acute myeloid leukemia with intermediate-risk cytogenetics and wild-type NPM1

Acute myeloid leukemia (AML) with myelodysplasia-related changes is characterized by the presence of multilineage dysplasia (MLD), frequently related to high-risk cytogenetics and poor outcome. However, the presence of MLD does not modify the favorable prognostic impact of NPM1 mutation. The prognosis of patients with AML presenting marked dysplasia lacking high-risk cytogenetics and NPM1 mutation is uncertain. We evaluated the prognostic impact of MLD in 177 patients with intermediate-risk cytogenetics AML (IR-AML) and wild-type NPM1. Patients were categorized as MLD-WHO (WHO myelodysplasia criteria; n?=?43, 24 %), MLD-NRW (significant MLD non-reaching WHO criteria; n?=?16, 9 %), absent MLD (n?=?80, 45 %), or non-evaluable MLD (n?=?38, 22 %). No differences concerning the main characteristics were observed between patients with or without MLD. Outcome of patients with MLD-WHO and MLD-NRW was similar, and significantly worse than patients lacking MLD. The presence of MLD (66 vs. 80 %, p?=?0.03; HR, 95 % CI?=?2.3, 1.08–4.08) and higher leukocyte count at diagnosis was the only variable associated with lower probability of complete remission after frontline therapy. Concerning survival, age and leukocytes showed an independent prognostic value, whereas MLD showed a trend to a negative impact (p?=?0.087, HR, 95 % CI?=?1.426, 0.95–2.142). Moreover, after excluding patients receiving an allogeneic stem cell transplantation in first CR, MLD was associated with a shorter survival (HR, 95 % CI?=?1.599, 1.026–2.492; p?=?0.038). In conclusion, MLD identifies a subgroup of patients with poorer outcome among patients with IR-AML and wild-type NPM1.     

Association of MCP-1-2518A/G polymorphism with susceptibility to autoimmune diseases: a meta-analysis

We performed a meta-analysis to estimate whether combined evidence shows the association between the MCP-1-2518A/G polymorphism and susceptibility to autoimmune diseases. Relevant articles dated to July 2014 were acquired from the PubMed, EMBASE, ISI, and CNKI databases. The number of the genotypes and/or alleles for the MCP-1-2518A/G in cases and control subjects was extracted, and statistical analysis was conducted using STATA 11.2 software. Summary odds ratios (ORs) with their 95 % confidence intervals (95 % CIs) were used to calculate the risk of autoimmune diseases with the MCP-1-2518A/G. Significant increased risk of autoimmune diseases could be found for A allele vs. G allele (OR?=?1.616, 95 % CI 1.027–2.542, P?=?0.038) and AA?+?AG vs. GG (OR?=?1.616, 95 % CI 1.027–2.542, P?=?0.038) in Asian patients with rheumatoid arthritis (RA), and for A allele vs. G allele (OR?=?1.383, 95 % CI 1.142–1.676, P?=?0.022) and AA vs. AG?+?GG (OR?=?1.575, 95 % CI 1.361–1.823, P?<?0.001) in European patients with Crohn’s disease (CD). In addition, when comparison of European patients with lupus nephritis (LN) and without LN, significant association between patients with LN and without LN also could be found for AA vs. AG?+?GG (OR?=?0.713, 95 % CI 0.545–0.933, P?=?0.014). This meta-analysis showed that the MCP-1-2518-A allele confers susceptibility to Asian patients with RA and European patients with CD.     

Polymorphisms of the glutathione S-transferases mu-1 (GSTM1) and theta-1 (GSTT1) and the risk of advanced alcoholic liver disease

Objective. The aim of this study was to determine whether null genotypes for glutathione transferase mu-1 (GSTM1) and theta-1 (GSTT1) influence the risk of development of advanced alcoholic liver disease. Material and methods. GSTM1 and GSTT1 genotypes were identified on DNA through multiple analysis with polymerase chain reaction in 153 subjects diagnosed with advanced alcoholic liver disease and in 241 healthy controls. Results. The frequency of the GSTM1 null genotype was not different between patients and controls (36.6% versus 41.1%, non-significant). The GSTT1 null genotype was more frequently found in patients than in controls (32% versus 22%, odds ratio 1.67, 95% CI 1.03–2.71, p=0.027). Moreover, patients were more likely to be simultaneous carriers of both GSTM1 and GSTT1 null genotypes (odds ratio 4.30, 95% CI 1.89–9.97, p=0.0003). Conclusions. The GSTT1 null genotype is more frequent among patients with advanced alcoholic liver disease than in controls. The coincidence of this genotype with the GSTM1 null genotype is four times more likely in patients. We suggest that polymorphisms affecting the activity of the glutathione S-transferase isoforms M1 and T1 may be associated with the risk of developing chronic severe ethanol liver damage.     

The relationship between factor V Leiden, prothrombin G20210A, and MTHFR mutations and the first major thrombotic episode in polycythemia vera and essential thrombocythemia

Arterial and venous thrombosis are the most frequent complications in patients with polycythemia vera and essential thrombocythemia. We sought to demonstrate a possible contribution of the factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) 677 C?>?T and 1298 A?>?C mutations to the thrombotic risk in patients with polycythemia vera and essential thrombocythemia along with other biological features of these patients. We included 86 patients with polycythemia vera, of which 34 (39.5 %) had major thrombosis and 95 patients with essential thrombocythemia, of which 22 (23.1 %) had major thrombosis. In the whole cohort of patients, only the factor V Leiden mutation was significantly associated with both arterial and venous thrombosis in univariate and multivariate analysis (odds ratio (OR)?=?4.3; 95 % confidence interval (CI)?=?1.5–12.5; p?=?0.008 and OR?=?4.3; 95 % CI?=?1.2–15.9; p?=?0.02, respectively). Other factors significantly associated with thrombosis in both univariate and multivariate analysis were male sex (OR?=?2.8, 95 % CI?=?1.4–5.4, p?=?0.002 and OR?=?3.5, 95 % CI?=?1.6–7.6, p?=?0.002, respectively) and the JAK2 V617F mutation (OR?=?5.5, 95 % CI?=?2.1–15, p?=?0.0001 and OR?=?6.9, 95 % CI?=?2.2–21.2, p?=?0.001, respectively). In conclusion, among the four mutations analyzed (factor V Leiden, prothrombin G20210A, and MTHFR 677 C?>?T and 1298 A?>?C), only factor V Leiden is a major contributor to thrombosis in polycythemia vera and essential thrombocythemia.     

Significant association between asthma risk and the GSTM1 and GSTT1 deletion polymorphisms: An updated meta‐analysis of case–control studies

Polymorphisms in GSTM1 and GSTT1 may be associated with asthma risk, yet several studies and meta‐analyses have reported inconclusive results. Therefore, an updated meta‐analysis was conducted. Literature searches were performed using the Pubmed, Embase and Web of Science databases until October 2012. Variant ‘null’ genotype was compared with wild‐type ‘present’ in the pooled data. All statistical analyses were performed using STATA 11.0. A total of 26 case–control studies were suitable for inclusion in the meta‐analysis. In the overall population, a significant association was found for both the GSTM1 (odds ratio (OR) = 1.452; 95% confidence interval (CI): 1.192–1.770) and GSTT1 polymorphism (OR = 1.792; 95% CI:1.293–2.483). For subgroup analysis by age, GSTM1 significantly increased risk for both children (OR = 1.368; 95% CI: 1.051–1.781) and adults (OR = 1.859; 95% CI: 1.183–2.921). For GSTT1, a significant association was only found in the adult population (OR = 2.312; 95%CI: 1.204–4.439). Based on subgroup analysis by ethnicity, a significant association for GSTM1 was found in Europe (OR = 1.303; 95% CI: 1.018–1.667), Africa (OR = 2.175; 95%CI: 1.560–3.031) and Latin America (OR = 2.265; 95%CI: 1.375–3.729). For GSTT1, significantly increased risk was found only for Asian (OR = 2.105; 95% CI: 1.101–4.025) and Russian (OR = 2.747; 95% CI: 1.071–7.046) populations. This meta‐analysis provides evidence that GSTM1 and GSTT1 polymorphisms may be risk factors for asthma.     

To drain or not to drain in colorectal anastomosis: a meta-analysis

Background

Currently, many surgeons place a prophylactic drain in the abdominal or pelvic cavity after colorectal anastomosis as a conventional treatment. However, some trials have demonstrated that this procedure may not be beneficial to the patients.

Objective

To determine whether prophylactic placement of a drain in colorectal anastomosis can reduce postoperative complications.

Methods

We systematically searched all the electronic databases for randomized controlled trials (RCTs) that compared routine use of drainage to non-drainage regimes after colorectal anastomosis, using the terms “colorectal” or “colon/colonic” or “rectum/rectal” and “anastomo*” and “drain or drainage.” Reference lists of relevant articles, conference proceedings, and ongoing trial databases were also screened. Primary outcome measures were clinical and radiological anastomotic leakage. Secondary outcome measures included mortality, wound infection, re-operation, and respiratory complications. We assessed the eligible studies for risk of bias using the Cochrane Risk of Bias Tool. Two authors independently extracted data.

Results

Eleven RCTs were included (1803 patients in total, 939 patients in the drain group and 864 patients in the no drain group). Meta-analysis showed that there was no statistically significant differences between the drain group and the no drain group in (1) overall anastomotic leakage (relative risk (RR)?=?1.14, 95 % confidence interval (CI) 0.80–1.62, P?=?0.47), (2) clinical anastomotic leakage (RR?=?1.39, 95 % CI 0.80–2.39, P?=?0.24), (3) radiologic anastomotic leakage (RR?=?0.92, 95 % CI 0.56–1.51, P?=?0.74), (4) mortality (RR?=?0.94, 95 % CI 0.57–1.55, P?=?0.81), (5) wound infection (RR?=?1.19, 95 % CI 0.84–1.69, P?=?0.34), (6) re-operation (RR?=?1.18, 95 % CI 0.75–1.85, P?=?0.47), and (7) respiratory complications (RR?=?0.82, 95 % CI 0.55–1.23, P?=?0.34).

Conclusions

Routine use of prophylactic drainage in colorectal anastomosis does not benefit in decreasing postoperative complications.

     

Meta-analysis of association between GSTM1 gene polymorphism and cervical cancer

ObjectiveTo investigate association between glutathione S-transferases (GSTs) and cervical cancer.MethodsPublished literature from PubMed, EMBASE, and other databases were retrieved. All studies evaluating the association between GSTM1/GSTT1 polymorphisms and cervical were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed- or random-effects model.ResultsA total of 15 case-control studies were included in the meta-analysis of GSTM1 genotypes (1 825 cases and 2 104 controls). The overall result showed that the association between GSTM1 null genotype and risk for cervical cancer was statistically significant (OR=1.53, 95%CI=1.18–2.00). Great heterogeneity was found between studies. Subgroup analysises were performed based on smoking and ethnicity. Our results showed that smokers with null GSTM1 genotype had higher risk of cervical cancer (OR=1.56, 95%CI=1.01–2.41). For the ethnicity stratification, significant increased risk of null GSTM1 genotype was found in Chinese and Indian population, but no increased risk in other population.ConclusionsThis meta-analysis provides strong evidence that the GSTM1 null genotype is associated with the development of cervical cancer, and especially in Chinese and Indian population, and smoking shows a modification on the association between GSTM1 null genotype and cervical cancer.     

Glutathione S-transferase M1 and T1 polymorphisms and cervical cancer risk: a meta-analysis

There were some studies on the associations between Glutathione S-transferase M1 (GSTM1) and Glutathione S-transferase T1 (GSTT1) polymorphisms and cervical cancer (CC) risk, but the results were inconsistent. Thus, a meta-analysis was performed. The electronic databases PubMed, Science Direct, CBM, and CNKI were searched for possible studies. Finally, 16 studies (1,627 cases and 2,161 controls) were included. For the GSTM1 and GSTT1 polymorphisms, the unadjusted odds ratios (OR) and 95% confidence intervals (95% CI) from each study were used to estimate summary OR. Subgroup analyses by ethnicity and histological type of CC were also performed. For the GSTM1 polymorphism, the null genotype of GSTM1 was associated with an increased CC risk in total population (OR=1.32, 95% CI=1.06-1.66). Similar association was found in Asians (OR=1.47, 95% CI=1.11-1.94), but not in Caucasians (OR=0.96, 95% CI=0.73-1.27). For the GSTT1 polymorphism, the null genotype of GSTT1 was not statistically significantly associated with CC risk in total population (OR=1.36, 95% CI=0.97-1.90). This result was also found in Asians (OR=1.27, 95% CI=0.87-1.85) and Caucasians (OR=1.09, 95% CI= 0.66-1.79), but not in Latinos (OR=4.58, 95% CI= 2.04-10.28). For the GSTM1/GSTT1 interaction analysis, the dual null genotypes of GSTM1/GSTT1 were significantly associated with increased CC risk in total population (OR=1.77, 95% CI= 1.14-2.75), and all the six studies were from Asia. For subgroup analyses by histological type of CC, the three aspects of the analyses above were all not significantly associated with CC risk in squamous cell carcinoma and adenocarcinoma, respectively. The null genotype of GSTM1 and the dual null genotypes of GSTM1/GSTT1 were risk factors in CC, and the null genotype of GSTT1 was not associated with CC risk.     

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.     

Glutathione S-transferase m1 and t1 null genotypes increase susceptibility to idiosyncratic drug-induced liver injury

Individual vulnerability to drug-induced liver injury (DILI) might result from deficiencies in the detoxification process, which determines the level of exposure to the reactive metabolite. We evaluated whether a genetically determined reduction in the ability to detoxify electrophilic compounds, such as that expected among individuals with glutathione S-transferase (GST) null genotypes, might play a role in determining the risk for DILI and its clinical expression. Genomic DNA from 154 patients (74 men, 80 women; mean age, 53 years) with a diagnosis of DILI as assessed with the Council for International Organizations of Medical Science scale and 250 sex- and age-matched healthy controls were analyzed. A multiplex polymerase chain reaction-based method was used to detect GSTM1 and GSTT1 gene deletions. Carriers of double GSTT1-M1 null genotypes had a 2.70-fold increased risk of developing DILI compared with noncarriers (odds ratio 2.70, 95% confidence interval 1.45-5.03; P = 0.003). The odds ratio for DILI patients receiving antibacterials, and NSAIDs were 3.52 (P = 0.002), and 5.61 (P = 0.001), respectively. Patients with amoxicillin-clavulanate hepatotoxicity (n = 32) had a 2.81-fold increased risk (P = 0.037). Patients classified by the combined GSTT1 and GSTM1 null genotypes did not differ with regard to the type of injury, clinical presentation, or outcome, except for the predominance of women in the combined null genotype (P < 0.001). CONCLUSION: The double-null genotype for GSTT1 and GSTM1 might play a role in determining the susceptibility to develop DILI, as a general mechanism that occurs regardless of the type of drug involved, and predominantly in women.     

Associations between <Emphasis Type="Italic">ERAP1</Emphasis> polymorphisms and susceptibility to ankylosing spondylitis: a meta-analysis

The aim of this study was to determine whether 11 polymorphisms of endoplasmic reticulum aminopeptidase 1 (ERAP1) confer susceptibility to ankylosing spondylitis (AS). The authors conducted meta-analyses on associations between ERAP1 polymorphisms and AS susceptibility by using fixed and random effects models. A total of 19 articles were included in this meta-analysis, which comprised a total of 19,902 AS patients and 39,750 controls. The meta-analysis revealed a significant association between AS and the minor alleles of the rs30187 polymorphism in all study subjects (OR?=?1.255, 95 % CI?=?1.147–1.373, P?=?8.0?×?10^?8). Stratification by ethnicity led to the identification of a significant association between this polymorphism and AS in European patients (OR?=?1.283, 95 % CI?=?1.237–1.331, P?<?1.0?×?10^?9). Meta-analyses of the results for the rs27044, rs10050860, rs2287987, rs17482078, and rs26653 polymorphisms showed the same pattern that was found for rs30187. Interestingly, the rs27037 polymorphism was significantly associated with AS susceptibility in both European and Asian patients. Meta-analysis showed a significant association between AS and the minor alleles of the rs27980 and rs27582 polymorphisms in the East Asian patients (OR?=?0.904, 95 % CI?=?0.818–0.999, P?=?0.047; OR?=?0.871, 95 % CI?=?0.772–0.982, P?=?0.024, respectively) (Table 2). However, these polymorphisms have not been studied in Europeans. This meta-analysis shows that the ERAP1 polymorphisms are associated with the development of AS in Europeans and East Asians.