Null Polymorphism Research Articles

Genetic polymorphisms in biotransformation enzymes for benzo[a]pyrene and related levels of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts in Goeckerman therapy.

Goeckerman therapy (GT) for psoriasis combines the therapeutic effect of crude coal tar (CCT) and ultraviolet radiation (UVR). CCT contains polycyclic aromatic hydrocarbons, some of which can form DNA adducts that may induce mutations and contribute to carcinogenesis. The aim of our work was to evaluate the relationship between concentrations of benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts (BPDE-DNA adducts) and rs4646903 (CYP1A1 gene), rs1048943 (CYP1A1), rs1056836 (CYP1B1), rs1051740 (EPHX1), rs2234922 (EPHX1) and rs8175347 (UGT1A1) polymorphic sites, and GSTM1 null polymorphism in 46 patients with chronic stable plaque psoriasis who underwent GT. The level of BPDE-DNA adducts was determined using the OxiSelect BPDE-DNA Adduct ELISA Kit. Polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (rs4646903, rs1048943, rs1051740, and rs2234922), fragment analysis (rs8175347), real-time PCR (rs1056836), and digital droplet PCR polymorphism (GSTM1) were used. CYP1B1*1/*1 wild-type subjects and CYP1B1*3/*1 heterozygotes for rs1056836 formed significantly higher amounts of BPDE-DNA adducts than CYP1B1*3/*3 homozygotes (p=0.031 and p=0.005, respectively). Regarding rs1051740, individuals with EPHX1*3/*1 heterozygosity revealed fewer adducts than EPHX1*1/*1 wild-type subjects (p=0.026). Our data suggest that CYP1B1/EPHX1 genotyping could help to predict the risk of DNA damage and to optimize doses of coal tar and UVR exposure in psoriatic patients in whom GT was applied.

Analysis of the glutathione S-transferase genes polymorphisms in the risk and prognosis of renal cell carcinomas. Case-control and meta-analysis

BackgroundThe Glutathione S-transferases (GSTs) genes deletion polymorphisms have been associated with the progression of several cancers. The association studies between the 2 GSTs (GSTM1 and GSTT1) null polymorphisms with the susceptibility to renal cell carcinoma (RCC) have been inconclusive. Therefore, with the inclusion of our own data, we performed a comprehensive meta-analysis to assess the association between these 2 polymorphisms and the risk of RCC. MethodsA systematic literature search was carried out for studies published in the PubMed, EMBASE, Cochrane library, and Google Scholar from 1997 to December 2014. Results were stated as pooled odds ratios (ORs) for nonparametric data after heterogeneity analysis with 95% CI using fixed effect or random effect model. ResultsWe systematically selected 13 relevant studies after thorough searches from the databases. Data showed no association between the GSTM1 and the GSTT1 null genotypes and the risk of RCC (OR = 1.01; CI: 0.92–1.11; P = 0.89 for GSTM1 and OR = 1.14; CI: 0.91–1.42; P = 0.25 for GSTT1). No association was found when the data were stratified according to the geographical/ethnic basis, source of control, and the risk factor evaluation. Subgroup analysis of occupational exposure to pesticides showed an inverse association of the active genotypes of both GSTM1 and GSTT1 polymorphisms with the exposed group of RCC (P<0.00001 and P<0.00001, respectively). The combined null genotype of the GSTM1/GSTT1 significantly increased the susceptibility to RCC by 1.4-fold (P = 0.001). This association remained significant for the Asian populations in subgroup analysis (OR = 1.8; CI: 1.30–2.49; P = 0.0004). ConclusionIn conclusion, this meta-analysis suggests that the 2 GSTs deletion polymorphisms independently have no association with the risk of RCC. However, combination of both deletions increases the risk of developing the RCC.

Associations Among Glutathione S-Transferase T1, M1, and P1 Polymorphisms and the Risk of Oral Leukoplakia.

The potential association between glutathione S-transferase (GST) M1, T1, P1 polymorphisms and the risk of oral leukoplakia (OLK) has been extensively studied. However, the results of previous studies have been contradictory. In an effort to resolve these different findings we performed a meta-analysis. Eligible articles were identified by a search of PubMed, the China National Knowledge Infrastructure (CNKI), MEDLINE, EMBASE, and the Web of Science databases through December 1, 2015. Crude odds ratios (ORs) with 95% confidence intervals were used to evaluate the risk of OLK by tobacco use, ethnicity, and OLK subtype. A total of 3122 cases and 6037 controls were included in the meta-analysis. The results indicated that the glutathione S-transferase Mu1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null polymorphisms increase the risk of OLK (OR = 1.838, 95% CI = 1.582-2.134 and OR = 1.337, 95% CI = 1.132-1.579, respectively), especially in the groups with tobacco use (OR = 2.478, 95% CI = 2.032-3.020 and OR = 2.034, 95% CI = 1.486-2.783, respectively). Conversely the glutathione S-transferase P1 (GSTP1) polymorphism did not demonstrate a significant relationship with OLK risk (OR = 1.139, 95% CI = 0.900-1.442). The GSTM1 and GSTT1 null polymorphisms were identified as being significantly associated with an increased risk of OLK within the German and Indian populations: German subgroup (GSTM1: OR = 11.555, 95% CI = 7.465-17.884), Indian subgroup (GSTM1: OR = 1.333, 95% CI = 1.084-1.638; GSTT1: OR = 1.332, 95% CI = 1.057-1.679). Our findings provide evidence that the GSTT1 and GSTM1 null polymorphisms may be risk factors of OLK, especially for persons who use tobacco, whereas the GSTP1 polymorphism does not contribute to the development of OLK. Thus, detection of GSTT1 and GSTM1 null polymorphisms may be promising biomarkers for the OLK susceptibility.

ACTN3 Genotype Affects Change in Muscle Fiber Cross-Sectional Area from Adolescence to Adulthood

INTRODUCTION: Alpha-actinin-3 is a Z-disc protein that is expressed only in type II muscle fibers. Common null polymorphism in the ACTN3 gene (R577X) results in lack of this protein in XX-genotypes. In sprint/power oriented elite athletes the prevalence of the X-allele is much lower than in control populations. That implies that lack of alpha-actinin-3 is detrimental for these athletes but a mechanistic link is not fully established. We have previously shown that ACTN3 genotype modulates skeletal muscle hypertrophy signaling in response to sprint exercise in moderately trained subjects. PURPOSE: To examine the impact of ACTN3 genotype on changes in fiber dimensions from adolescence to adulthood. METHODS: 63 male and female subjects (13 XX, 29 RX, 21 RR) from the general Swedish population were studied at 16 and 27 years of age. Their physical activity level was estimated by a questionnaire. Muscle samples were obtained from vastus lateralis muscle by needle biopsy technique. The samples were analyzed histochemically for fiber types (I, IIA, IIB). Cross-sectional area (CSA) of the different fiber types was measured from histological sections by planimetry. DNA was extracted from muscle samples and the genotyping was performed by allelic discrimination. Statistical analyses of the effect of ACTN3 and sex on changes in CSA with age were performed by ANOVA and multiple regression analysis. RESULTS: A significant difference in the relative change of CSA with age, across ACTN3 genotypes was observed in type IIA fibers (ANOVA P=0.02) but not in type I fibers and type IIB fibers. The change, expressed as 27-16 years/16-years value, was in type IIA fibers -4.2%, -2.5% and 7.7% in XX, RX and RR respectively and in type IIB -3.0%, -3.4%, and 9.9% in XX, RX and RR respectively. Multiple regression analysis showed that the change in CSA of type IIA fibers was dependent on ACTN3 genotype, while the change in CSA of type IIB was equally dependent on ACTN3 genotype and sex. No ACTN3 genotype effect was observed for the CSA change in type I fibers where alpha-actinin-3 is not expressed. No significant differences in CSA were detected across ACTN3 genotypes either at 16 or 27 years. CONCLUSION: ACTN3 genotype is strongly suggested to be a determinant of dimensions of type II skeletal muscle fibers in humans which supports the findings in ACNT3 knock out mice.

Association of DNA repair and xenobiotic pathway gene polymorphisms with genetic susceptibility to gastric cancer patients in West Bengal, India.

Gastric cancer is one of the most common malignancies in India. DNA repair gene or xenobiotic pathway gene polymorphisms have recently been shown to affect individual susceptibility to gastric cancer. Here, the possible interaction between common polymorphisms in X-ray repair cross complementing group I (XRCC1) gene and glutathione S-transferase (GST) genes (GSTM1, GSTT1 and GSTP1), smoking and alcohol consumption and overall survival in gastric cancer patients were evaluated. In this population-based case control study, 70 gastric cancer patients and 82 healthy controls were enrolled. The epidemiological data were collected by a standard questionnaire, and blood samples were collected from each individual. XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms were determined by polymerase chain reaction and direct DNA sequencing. GSTM1 and GSTT1 null polymorphisms and GSTP1 Ile105Val polymorphism were identified by multiplex polymerase chain reaction and restriction fragment length polymorphism (RFLP), respectively. The risk of gastric cancer was significantly elevated in individuals with XRCC1 Arg/Gln +Gln/Gln (p = 0.031; odds ratio = 2.32; 95% confidence interval (CI) 1.07-5.06) and GSTP1 Val/Val genotype (p = 0.009; odds ratio = 8.64; 95% CI 1.84-40.55). An elevated risk for GC was observed in smokers and alcohol consumers carrying GSTP1 Ile/Val +Val/Val genotype (p = 0.041; odds ratio = 3.71; 95% CI 0.98-14.12; p = 0.002; odds ratio = 12.31; 95% CI 1.71-88.59). These findings suggest that XRCC1 rs25487 and GSTP1 rs1695 can be considered as a risk factor associated with gastric cancer and might be used as a molecular marker for evaluating the susceptibility of the disease.

Glutathione S-transferase M1 Polymorphism and Breast Cancer Risk: a Meta-Analysis in the Chinese Population

Published data on the association between present/null polymorphism of glutathione S-transferase M1 (GSTM1) and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis in the Chinese population was performed. PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association between the GSTM1 present/ null polymorphism and breast cancer risk. A total of 17 studies including 5323 breast cancer cases and 7196 controls were involved in this meta-analysis. Overall, a significant association (OR = 1.28, 95%CI: 1.09 - 1.51) was found between the null GSTM1 and breast cancer risk when all studies in Chinese population were pooled into the meta-analysis. In subgroup analyses stratified by geographic areas and source of controls, the same results were observed in mainland China (OR = 1.42, 95% CI = 1.12 - 1.81) and hospital-based studies (OR = 1.55, 95% CI = 1.20 - 2.00). This meta-analysis suggests that the GSTM1 null genotype is a low-penetrant risk factor for developing breast cancer in the Chinese population.

GSTM1 null polymorphism prevalence in tobacco users, oral leukoplakia and oral squamous cell carcinoma patients in South Indian population: A polymerase chain reaction study.

Tobacco abuse is a well-known risk factor for potentially malignant disorders as well as oral squamous cell carcinoma. Factors that influence tobacco-exposed individuals developing a malignancy may include the combination of total tobacco exposure and genetic susceptibility. This study was undertaken to determine the prevalence of the glutathione S-transferase M1 (GSTM1) null polymorphism in oral leukoplakia and oral squamous cell carcinoma patients in South Indian population. This case-control study was conducted in hospital setting on South Indian population. About 280 subjects with history of tobacco use, oral leukoplakia, oral squamous cell carcinoma were included in this study. Three milliliter of blood was collected and transported under cold cycle and taken for evaluation of GSTM1 null polymorphism using multiplex polymerase chain reaction. On comparing the prevalence of GSTM1 null polymorphism among the group with subjects with habits and no oral lesions, oral leukoplakia, and oral squamous cell carcinoma, it was observed that there was a statistically significant association between GSTM1 null polymorphism and the different groups (P < 0.01). The lack of GSTM1 activity would make the oral tissues more susceptible to action of tobacco carcinogens and to the development of a high-grade level of dysplasia in oral leukoplakia and thereby increases the susceptibility of lesion to undergo malignant changes.

Null Single Nucleotide Polymorphism in Chemokine Receptor 5 (CCR5) Genes among the Ijaw Ethnic Population of Nigeria

Background: A deletion of 32 bp in the nucleotide sequence of CCR5 gene results in a defective CCR5 which confers protection from HIV infection in the homozygous state, while reducing the rate of disease progression to AIDS and death in the heterozygous state. The status of the CCR5Δ32 gene has not been reported in Nigeria. Aim: This study was aimed at analyzing single nucleotide polymorphism of CCR5 gene among the Ijaws resident in Yenagoa, Nigeria. Methods: 100 subjects (75 HIV negative and 25 HIV positive control) were recruited for this study. The CCR5 genes were amplified by 2 Stage PCR reaction using GeneAmp 9700 PCR system utilizing specific primers that would flank 32 bp deletion, followed by agarose gel electrophoresis, DNA sequencing of 20 subjects was done followed by phylogenetic and polymorphism analysis. Results: The results showed that 75 (100%) of the HIV negative subjects had 189 base pair in their CCR5 gene. Nucleotide of the 20 (100%) of the sequenced samples were conservatively same and no SNP was observed. Conclusion: This study documented no SNPs in CCR5 gene of the study population hence; the study population has no protection from HIV infection.

NADPH: Quinone oxidoreductase 1 (NQO1609C&gt;T) Polymorphism and Gastric Cancer Risk: A Meta-Analysis

Evidence is increasingly emerging about multiple roles for the NAD (P) H quinine oxidoreductase 1 (NQO1) enzyme in gastric cancer (GC). The NQO1609C>T (Pro187Ser) null polymorphism of the NQO1 gene contributes significantly to the variation in enzymatic activity across different populations. NQO1609C>T polymorphism was thoroughly investigated with respect to gastric cancer susceptibility. The results were inconsistent partly due to low sample sizes. The aim of the present work was to perform a meta-analysis to assess association for gastric cancer. Present meta-analysis involved eligible studies including 722 cases and 853 controls. Present metaanalysis found a statistically significant association between the variant T allele and overall cancer risk in the worldwide population (for the TT vs CC; co-dominant model, OR=1.568; 95%CI=1.096-2.244; P=0.014). At allele level, NQO1609C>T polymorphism was significantly correlated with increased GC risk (OR=1.302; 95%CI=1.111-1.525; P=0.001). In subgroup analysis positive association was also found for gastric cancer in recessive (OR=1.456; 95%CI=1.050-2.020; P=0.024) model. Stratified analysis revealed that this association was largely attributed to the Assian ethnicity (for the TT vs CC model, OR=1.227; 95%CI=1.022-1.473; P=0.028). Present results indicate that the 609C>T polymorphism of the NQO1 gene is an important genetic risk factor in gastric cancer.

Glutathione S-transferase M1 polymorphism and esophageal cancer risk: An updated meta-analysis based on 37 studies.

To evaluate the relationship between glutathione S-transferase M1 (GSTM1) polymorphism and susceptibility to esophageal cancer (EC). A comprehensive search of the United States National Library of Medicine PubMed database and the Elsevier, Springer, and China National Knowledge Infrastructure databases for all relevant studies was conducted using combinations of the following terms: "glutathione S-transferase M1", "GSTM1", "polymorphism", and "EC" (until November 1, 2014). The statistical analysis was performed using the SAS software (v.9.1.3; SAS Institute, Cary, NC, United States) and the Review Manager software (v.5.0; Oxford, England); crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between the GSTM1 null genotype and the risk of EC. A total of 37 studies involving 2236 EC cases and 3243 controls were included in this meta-analysis. We observed that the GSTM1 null genotype was a significant risk factor for EC in most populations (OR = 1.33, 95%CI: 1.12-1.57, P heterogeneity < 0.000001, and I (2) = 77.0%), particularly in the Asian population (OR = 1.53, 95%CI: 1.26-1.86, P heterogeneity < 0.000001, and I (2) = 77.0%), but not in the Caucasian population (OR = 1.02, 95%CI: 0.87-1.19, P heterogeneity = 0.97, and I (2) = 0%). The GSTM1 null polymorphism may be associated with an increased risk for EC in Asian but not Caucasian populations.

GSTT1 Null Genotype Significantly Increases the Susceptibility to Urinary System Cancer: Evidences from 63,876 Subjects

GSTT1 gene plays an important role in detoxification and clearance of reactive oxygen species(ROS). A null variant in this gene has been demonstrated to confer cancer susceptibility. Although many studies have demonstrated the association between GSTT1 null polymorphism and urinary system cancer susceptibility, several publications reported opposite conclusions. For better understanding the effects of this polymorphism on the risk of urinary system cancer, a updated meta-analysis was performed with a total of 26,666 cases and 37,210 controls extracted from 117 studies, by following the latest meta-analysis guidelines (PRISMA). The results suggested that the GSTT1 null genotype was significantly associated with an increased risk of urinary system cancer (OR=1.13, 95%CI=1.05-1.22). Furthermore, stratified analyses by the type of cancer, ethnicity, source of control and quality score presented a significantly increased risk associated with GSTT1 null genotype in bladder and prostate cancer subgroup, Caucasians and Indians subgroup, population-based(PB) subgroup, medium quality and low quality subgroup. Overall, our meta-analysis suggested that GSTT1 null genotype is a potential cancer susceptibility variant. Well-designed and large-cohort studies are needed to confirm the association between GSTT1 null genotype and urinary system cancer risk.

Analysis of the ACTN3 heterozygous genotype suggests that α-actinin-3 controls sarcomeric composition and muscle function in a dose-dependent fashion.

A common null polymorphism (R577X) in ACTN3 causes α-actinin-3 deficiency in ∼ 18% of the global population. There is no associated disease phenotype, but α-actinin-3 deficiency is detrimental to sprint and power performance in both elite athletes and the general population. However, despite considerable investigation to date, the functional consequences of heterozygosity for ACTN3 are unclear. A subset of studies have shown an intermediate phenotype in 577RX individuals, suggesting dose-dependency of α-actinin-3, while others have shown no difference between 577RR and RX genotypes. Here, we investigate the effects of α-actinin-3 expression level by comparing the muscle phenotypes of Actn3(+/-) (HET) mice to Actn3(+/+) [wild-type (WT)] and Actn3(-/-) [knockout (KO)] littermates. We show reduction in α-actinin-3 mRNA and protein in HET muscle compared with WT, which is associated with dose-dependent up-regulation of α-actinin-2, z-band alternatively spliced PDZ-motif and myotilin at the Z-line, and an incremental shift towards oxidative metabolism. While there is no difference in force generation, HET mice have an intermediate endurance capacity compared with WT and KO. The R577X polymorphism is associated with changes in ACTN3 expression consistent with an additive model in the human genotype-tissue expression cohort, but does not influence any other muscle transcripts, including ACTN2. Overall, ACTN3 influences sarcomeric composition in a dose-dependent fashion in mouse skeletal muscle, which translates directly to function. Variance in fibre type between biopsies likely masks this phenomenon in human skeletal muscle, but we suggest that an additive model is the most appropriate for use in testing ACTN3 genotype associations.

Evaluating molecular study of the association of Glutathione S – Transferase GST (T1 , M1) genetic polymorphism in Iraqi Arab Femals with Type 2 Diabetes Mellitus and Coronary Artery Disease

Coronary artery disease (CAD) is a major health concern and leading of death in individuals with type 2 diabetes mellitus (T2DM). Glutathione S – Transferase(GST) are known for their broad range of detoxification and in the metabolism of xenobiotics . The role of functional variants of these genes in the development of various disorder is proven. We investigated the possible role of these variants in the development of CAD in T2DM patients. In this case – control study a total of 60 patients (T2DM = 30 ; T2DM – CAD = 30) and 30 controls were included. Serum lipid profiles were measured and DNA was extracted from the blood samples. Multiplex PCR for GSTT1/M1 (present / null) polymorphism, were performed for genotyping of study participants. Gene frequency and lipid profiles were statistically analyzed for disease association. Regression analysis showed that, there was no significant difference of the frequency of GSTT1 (positive /null) genotype and GSTM1 (positive /null) genotype in the 3 study groups . GSTT1 – positive genotype is associated with a 0.51 fold increased ( OR = 0.51 ; 95%CI = 2- 0.1 ;P = 0.321 ) , while the GSTM1 – positive genotype was associated with a 3 fold increase ( OR = 3.06 ; 95%CI=1- 9.7 ; P = 0.055) .We conclude GSTT1 positive genotype considered to be a protective risk from CAD in T2DM patients . The GSTM1 – positive genotype it was considered to be a risk factor of the CAD in T2DM patients.

Evaluating molecular study of the association of Glutathione S – Transferase GST (T1 , M1) genetic polymorphism in Iraqi Arab Femals with Type 2 Diabetes Mellitus and Coronary Artery Disease

Coronary artery disease (CAD) is a major health concern and leading of death in individuals with type 2 diabetes mellitus (T2DM). Glutathione S – Transferase(GST) are known for their broad range of detoxification and in the metabolism of xenobiotics . The role of functional variants of these genes in the development of various disorder is proven. We investigated the possible role of these variants in the development of CAD in T2DM patients. In this case – control study a total of 60 patients (T2DM = 30 ; T2DM – CAD = 30) and 30 controls were included. Serum lipid profiles were measured and DNA was extracted from the blood samples. Multiplex PCR for GSTT1/M1 (present / null) polymorphism, were performed for genotyping of study participants. Gene frequency and lipid profiles were statistically analyzed for disease association. Regression analysis showed that, there was no significant difference of the frequency of GSTT1 (positive /null) genotype and GSTM1 (positive /null) genotype in the 3 study groups . GSTT1 – positive genotype is associated with a 0.51 fold increased ( OR = 0.51 ; 95%CI = 2- 0.1 ;P = 0.321 ) , while the GSTM1 – positive genotype was associated with a 3 fold increase ( OR = 3.06 ; 95%CI=1- 9.7 ; P = 0.055) .We conclude GSTT1 positive genotype considered to be a protective risk from CAD in T2DM patients . The GSTM1 – positive genotype it was considered to be a risk factor of the CAD in T2DM patients.

GSTT1 and GSTM1 polymorphisms predict treatment outcome for breast cancer: a systematic review and meta-analysis.

Observational studies have reported controversial results on the association between GSTT1 and GSTM1 genotypes and treatment outcome of breast cancer. The purpose of this study is to evaluate the association between GSTT1 and GSTM1 and treatment outcome in breast cancer patients. Eligible studies were searched in PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure databases. A random-effect model or fixed-effect model was used to calculate the overall combined risk estimates. Twenty-one studies with a total of 4990 patients were included in this meta-analysis. The GSTM1 null genotype (odds ratio (OR) = 1.33, 95% confidence interval (CI) 1.01-1.75, P = 0.046) and GSTT1/GSTM1 double null genotype (OR = 2.22, 95% CI 1.02-4.84, P = 0.045) were significantly associated with an increased tumor response. A reduced overall survival (hazard ratio (HR) = 0.84, 95% CI 0.72-0.98, P = 0.024) was observed in GSTM1 null genotype, especially in mixed descent (HR = 0.77, 95% CI 0.61-0.96, P = 0.018) and large sample size (HR = 0.85, 95% CI 0.72-0.99, P = 0.033). Evidence of publication bias was observed in GSTM1 genotype rather than in GSTT1 genotype. This meta-analysis suggests that GSTM1 null and GSTT1/GSTM1 double null polymorphisms might be significantly associated with an increased tumor response. However, the GSTM1 null genotype might be significantly associated with a reduced overall survival. Future studies are warranted to confirm these findings.

Frequency of Class I common or well documented null alleles in National Marrow Donor Program high resolution typing programs

Aim NMDP high resolution (HR) testing programs require typing for common or well documented (CWD) null alleles in alignment with Mack et al., Tissue Antigens. 2013: 81(4): 194–203 (CWD 2.0). The aim of this study was to determine the frequency of CWD 2.0 Class I null alleles in NMDP HR typing programs and whether these alleles occur outside of their expected haplotypes. Methods Labs performing HR typing routinely test exons 2–4, then additional regions depending on where a CWD null allele polymorphism is located. Typing methods include SSO, SBT, and NGS. HR Class I typing results from historic adult donor registry samples and CBU samples performed in 2013–2015 were queried for reports of CWD null alleles. Results Four different Class I CWD null alleles were reported a total of 35 times in 41,864 tests. B∗51:11N is expected in the A∗02∼DRB1∗04 haplotype but was observed in A∗03:01∼C∗07:02∼DRB1∗04:02. C∗04:09N was observed with its most common haplotype A∗23:01∼B∗44:03∼DRB1∗07:01 in 53% of cases and with B∗44 in 100% of cases. The common A∗02:53N was not reported; it occurs in up to 0.10% of Chinese populations. The remainder of the CWD nulls were not observed. G group frequency is the null allele frequency within the two digit G group typing. Conclusion Although the frequency of Class I CWD null alleles in the queried HLA results is low, they may warrant continued routine typing. Failure to identify a null allele results in a hidden mismatch between donor and patient. However, lab costs increase due to the additional typing required to detect polymorphisms located outside of exons 2–3. As exon 7 is not routinely tested, typing for C∗04:09N only in the presence of B∗44 may be a future consideration for NMDP HR contracts and policies. Download : Download full-size image

GSTM1 polymorphism contribute to colorectal cancer in Asian populations: a prospective meta-analysis.

Glutathione S-transferases (GSTs) are enzymes which expressed in many tissues and play important roles in neutralization of toxic compounds, and protecting hosts against cancer. Among several GSTs, Glutathione S-transferases mu (GSTM) has been drawn attention upon the association with the genetic risk for many types of cancers. But whether the GSTM1 polymorphisms confer the susceptibility to colorectal cancer in Asians has not been well established. We searched the PubMed database with GSTM1, polymorphism and colorectal cancer, attempting to identify the eligible studies. In total, 33 case-control studies in Asian populations with 8502 colorectal cancer patients and 13699 controls were included in the current meta-analysis. The association between the polymorphism and susceptibility to colorectal cancer was evaluated by the odds ratio (OR) and 95% confidence intervals (CI). The pooled meta-analysis suggested that GSTM1 null variant was correlated to the colorectal cancer risk in Asians. There was a marginal heterogeneity among these eligible studies. Nevertheless, cumulative meta-analysis observed a trend of an obvious association between the GSTM1 null genotype and colorectal cancer risk in Asians. In summary, the meta-analysis suggested that GSTM1 null polymorphism confer the susceptibility to colorectal cancer in Asians, especially in Chinese populations.

Is there association between Glutathione S Transferases polymorphisms and cataract risk: a meta-analysis?

BackgroundGlutathione S transferase (GST) polymorphisms have been considered as risk factors for age-related cataracts, but the results remain controversial. In this study, we have performed a meta-analysis to evaluate the association between polymorphisms of GSTM1 and GSTT1 and cataract risk.MethodsPublished literature from PubMed and other databases were retrieved. The case–control studies regarding the association between GSTM1 or GSTT1 polymorphism and cataract risk were included. Pooled odds ratio (OR) and 95 % confidence interval (CI) were calculated using random- or fixed-effects model.ResultsFifteen studies on GSTM1 (3,065 patients and 2,105 controls), and nine studies on GSTT1 (2,374 patients and 1,544 controls) were included. By pooling all the studies, GSTM1 null polymorphism was not associated with cataract risk, and this negative association maintained in subgroup analyses. However, GSTT1 null polymorphism was significantly associated with increased risk of posterior subcapsular (OR, 1.42; 95 % CI, 1.04–1.94) but not other subtypes of cataract. Stratified analyses demonstrated an association of GSTT1 null genotype with increased risk of cataract in Asian (OR, 1.44; 95 % CI, 1.14–1.83) but not Caucasian populations. In addition, seven pooled studies showed no association of cataract risk with the combined GSTM1 and GSTT1 null genotypes.ConclusionsThis meta-analysis suggests that GSTT1 null polymorphism is associated with increased risk of posterior subcapsular cataract. Given the limited sample size, the association between GSTT1 null polymorphism and cataract risk in Asian awaits further investigation.

Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) null polymorphisms and the risk of hypertension: a meta-analysis.

BackgroundSome studies have recently focused on the association between glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null polymorphisms and hypertension; however, results have been inconsistent.ObjectiveIn order to drive a more precise estimation, the present systematic review and meta-analysis is performed to investigate the relationship between the GSTM1 and GSTT1 null polymorphisms and hypertension.MethodsEligible articles were identified by a search of several bibliographic databases for the period up to August 17, 2013. Odds ratios were pooled using either fixed-effects or random-effects models.ResultsRegarding the GSTM1 null/present genotype, 14 case—control studies were eligible (2773 hypertension cases and 3189 controls). The meta-analysis revealed that it might present a small increased risk for hypertension, although the effect was not statistically significant (odd ratio (OR) = 1.16, 95% confidence interval (CI): 0.96, 1.40; P = 0.002, I2 = 59.8%). Further subgroup analysis by ethnicity and control source suggested that the association was still not significant. Thirteen case—control studies were eligible for GSTT1 (2497 hypertension cases and 3078 controls). No statistically significant association was observed between the GSTT1 null genotype and hypertension risk (OR = 1.14, 95% CI: 0.85, 1.53; P = 0.000, I2 = 80.3%). Furthermore, stratification by ethnicity and control source indicated no association between the GSTT1 null genotype and hypertension risk. We further confirmed the association by sensitivity analysis. No publication bias was detected.ConclusionThis meta-analysis suggests that the GSTM1 and GSTT1 null polymorphisms are not associated with the risk of hypertension. Future large well-designed epidemiological studies with individual information, lifestyle factors, and environmental factors are warranted to validate the present findings.

GSTM1 Null Genotype and GSTP1 Ile105Val Polymorphism Are Associated with Alzheimer's Disease: a Meta-Analysis.

Published studies on the associations between glutathione S-transferase (GST) polymorphisms and Alzheimer's disease reported controversial findings. A meta-analysis of published studies was performed to assess the associations between polymorphisms of GSTM1, GSTT1 and GSTP1, and Alzheimer's disease. PubMed, Embase, and other databases were searched for case-control on the associations between polymorphisms of GSTM1, GSTT1 and GSTP1, and Alzheimer's disease. The odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the associations. Eleven articles were finally included into the meta-analysis, including eight studies on GSTM1 null genotype, six studies on GSTT1 null genotype, and six studies on GSTP1 Ile105Val polymorphism. Overall, GSTM1 null genotype was associated with increased risk of Alzheimer's disease (fixed effect OR = 1.34, 95% CI 1.10-1.64, P = 0.004). GSTT1 null genotype was not associated with risk of Alzheimer's disease (random effect OR = 1.15, 95% CI 0.68-1.92, P = 0.60). Besides, GSTP1 Ile105Val polymorphism was significantly associated with increased risk of Alzheimer's disease (Val vs Ile: OR = 1.45, 95% CI 1.05-1.99, P = 0.023; ValVal vs IleIle: OR = 1.87, 95% CI 1.30-2.69, P = 0.001; ValVal vs IleIle + IleVal: OR = 1.76, 95% CI 1.24-2.51, P = 0.002). No obvious risk of publication bias was observed in the meta-analysis. GSTM1 null genotype and GSTP1 Ile105Val polymorphism are associated with increased risk of Alzheimer's disease. More studies with large sample size are needed to validate the findings in the meta-analysis.