Frequency Of GSTM1 Research Articles

Glutathione-S-transferase (GSTM1 and GSTT1) polymorphism and lead toxicity in individuals environmentally exposed to lead

Genetic variation in enzymes involved in metal detoxification could have influence on susceptibility to lead-induced oxidative stress. The present study aimed at evaluating the effects of genetic variation of Glutathione-S- transferase gene on oxidative stress markers (GSH, SOD, CAT and MDA) among individuals environmentally exposed to lead. GSTM1 and GSTT1 null homozygous genotypes were determined by polymerase chain reaction. Blood lead levels were determined using Microwave Plasma Atomic Emission Spectroscopy (MP- AES-Agilent 4210 USA). Activities of superoxide dismutase, catalase and glutathione levels were assayed using Cayman’s commercial kits. The study found mean blood lead levels of the study subjects of 78.16± 5.79µg/dl with range from 26.6 to 191.0 µg/dl. The frequencies of GSTM1 and GSTT1 null genotypes were 23% and 50.8% respectively. The frequency was high in individuals with blood lead levels greater than 70µg/dl. Significant decreased activity of antioxidant enzymes (SOD and CAT), glutathione levels and concomitant increased of MDA concentrations were observed in individuals with GSTM1 and GSTT1 null genotypes. Therefore, findings from this study were enough to infer a causal relationship between environmental exposure to lead and oxidative stress. Individuals who are homologous null at GSTM1 and GSTT1 loci predispose to increased risk of multi-organs toxicity from environmental exposure to lead.

Frequency of null genotypes of glutathione S-transferase M1 and T1 in Japanese patients with drug-induced liver injury.

Previous reports suggest that the null genotype (*0/*0) of glutathione S-transferase (GST) M1 and/or GSTT1 could be risk factors for drug-induced liver injury (DILI). However, multi-institutional pharmacogenetic research with various suspected drugs has rarely been performed in Japan. Therefore, the aim of this study was to investigate the role of GSTM1 and GSTT1 null genotype in the occurrence of DILI in Japanese patients. Blood samples of 270 DILI patients from 23 hospitals throughout Japan collected between 2010 and 2018 were subjected to genotyping of null genotypes of GSTM1 and GSTT1 using the SmartAmp-2 method. We also collected information on DILI types, time to onset of DILI, pharmacological classification of suspected drugs and Digestive Disease Week-Japan score, as well as genotypes of GSTM1 and GSTT1 in each patient with DILI. The distribution of a combination of null genotypes of GSTM1 and GSTT1 in Japanese patients with DILI was significantly different from that reported in the general Japanese population. Notably, the incidence of the GSTM1 null genotype in patients with DILI was significantly higher than that of the control population. A significant relationship between the frequency of GSTM1 and GSTT1 null genotypes and pharmacological classification of suspected drugs, clinical laboratory data for liver function, time to onset of DILI, and Digestive Disease Week-Japan scores was not observed. The GSTM1 null genotype was associated with an increased incidence of DILI in Japanese patients.

Association of GSTM1 and GSTT1 gene polymorphisms with COVID-19 susceptibility and its outcome.

Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has become a global health issue and develops into a broad range of illnesses from asymptomatic to fatal respiratory diseases. SARS‐CoV‐2 infection is associated with oxidative stress that triggers cytokine production, inflammation, and other pathophysiological processes. Glutathione‐S‐transferase (GST) is an important enzyme that catalyzes the conjugation of glutathione (GSH) with electrophiles to protect the cell from oxidative damage and participates in the antioxidant defense mechanism in the lungs. Thus, in this study, we investigated the role of GSTM1 and GSTT1 gene polymorphism with COVID‐19 susceptibility, as well as its outcome. The study included 269 RT‐PCR confirmed COVID‐19 patients with mild (n = 149) and severe (n = 120) conditions. All subjects were genotyped for GSTM1 and GSTT1 by multiplex polymerase chain reaction (mPCR) followed by statistical analysis. The frequency of GSTM1−/−, GSTT1−/− and GSTM1−/−/GSTT1−/− was higher in severe COVID‐19 patients as compared to mild patients but we did not observe a significant association. In the Cox hazard model, death was significantly 2.28‐fold higher in patients with the GSTT1−/− genotype (p = 0.047). In combination, patients having GSTM1+/+ and GSTT1−/− genotypes showed a poor survival rate (p = 0.02). Our results suggested that COVID‐19 patients with the GSTT1−/− genotype showed higher mortality.

Frequency and Association Of GSTM1 and GSTT1 Gene Polymorphisms with Survival in Breast Cancer Patients.

Objective:Glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) are the key detoxification enzymes of xenobiotics, including chemotherapeutic drugs. The deletion polymorphisms of GSTM1 and GSTT1 genes are associated with reduced enzyme activity that influenced clinical outcomes of chemotherapeutic agents in breast cancer. However, there is limited information among Thai patients. This research aims to explore the frequency and role of GSTM1 and GSTT1 polymorphisms on survival among Thai patients with breast cancer. Methods: The retrospective cohort study was performed. Demographic data and clinicopathology characteristics were collected from hospital base registry data and medical records. A multiplex qualitative real-time PCR method was used to detect the presence or absence of the GSTM1 and GSTT1 gene in the genomic DNA samples of the participants. Results:The frequencies of the GSTM1 and GSTT1 null genotypes in 198 breast cancer patients were 65.70% and 33.30%, respectively. The overall survival at 1, 3 and 5 years were 95.00%, 83.00%, 71.00% respectively. The log rank test and Cox proportional hazards revealed a significant different in the 5-years overall survival according to lymph node metastasis and tumor stage (P = 0.014 and P < 0.001). No associations between overall survival and GSTM1 or GSTT1 genotype were found in single or combined genotypes analyses (P = 0.76 and P= 0.15). Conclusion:The results of our study provided the epidemiological information for prognostic of survival in breast cancer patients treated with chemotherapy.

The impact of GSTM1 and GSTT1 polymorphisms on susceptibility to gestational diabetes in Iranian population

Background Gestational diabetes mellitus (GDM) is characterized as a common metabolic disorder during pregnancy which is associated with glucose intolerance and insulin resistance. Genetic predisposition could contribute to the development of GDM. Methods We conducted a case-control study to inspect the impact of GSTM1 and GSTT1 polymorphism on GDM susceptibility in Iranian population. The population consisted of 149 pregnant women with GDM as cases, and 138 healthy pregnant women without any history of GDM as controls. Polymerase chain reaction-restriction fragment length polymorphism method was applied to determine the GSTM1 and GSTT1 gene polymorphisms. Results There were statistically significant differences between the cases and controls in terms of age (p = .005), BMI (p < .001), family history of gestational diabetes (p < .001), FBS (p = .001), TG (p ≤ .001), and HDL (p = .003). However, no significant differences were observed in TC (p = .078) and LDL (p = .062). There were significant differences between GSTM1 polymorphism (Null and present) in the case and controls groups [OR (95% CI); 2.3 (1.4–3.7), p < .001]. The distribution of GSTM1-null genotype was found to be significantly higher in GDM patients (68.6%) than the control group (48.5%). No significant variance was detected between GSTT1 polymorphism (Null and present) in the case and controls groups [OR (95% CI); 1.1 (0.6–1.6), p = .088]. The frequency of GSTM1 null/GSTT1 null [OR (95% CI); 2.7 (1.2–5.2), p = .01] and GSTM1 null/GSTT1 present [OR (95% CI); 2.6 (1.4–4.8), p = .002] genotypes significantly differed between the GDM and control groups. Conclusion It seems that GSTM1 null genotype might be considered as GDM risk factor in Iranian population.

GSTM1 and GSTT1 Polymorphisms and Susceptibility to Acute Myeloid Leukemia: A Case-control Study of the Sudanese Population

Background: Glutathione S-transferase (GST) enzyme levels are associated with risk of many types of cancers, including hematological malignancies. In this study we here aimed to investigate the relationship between GSTM1 and GSTT1 polymorphisms and the risk of AML. Conflicts in the published results and the absence of similar in-depth studies in Sudan prompted us to perform the present case-control study to determine the frequency of GSTM1 and GSTT1 polymorphisms in AML patients and their possible association with AML in a Sudanese population.Materials and Methods: A total of 40 patients with AML and 40 control subjects were enrolled in this study. Blood samples were collected from all patients in EDTA containing tubes. Genomic DNA was extracted from all blood samples using salting out method. Genotyping for detection of GSTM1, and GSTT1 polymorphisms was performed for both patients and controls using a multiplex PCR. Results: We reported that there is an association between the GSTM1 null genotype and AML risk (OR= 2.7, 95% CI= 1.2-6.04; P.value = 0.012), the GSTT1 null genotype appeared also to have an influence in the development of AML (OR= 4.93, 95% CI= 1.6-15.07; P.value = 0.005).Conclusion: These findings indicate that genetic variants of GSTM1 and GSTT1 genes may increase individual susceptibility to AML.

GSTM1 and GSTT1 copy number variants and the risk to Thai females of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignancy found throughout the world that most often occurs in males. The cancer is associated with many risk factors such as viral infection, cirrhosis, alcohol, smoking, and fungal toxins. GSTM1 and GSTT1 are detoxification enzymes activated by the cleansing of carcinogenic compounds. Low DNA copy numbers of Glutathione S-transferases M1 and T1 result in a loss of enzyme activity, which causes carcinogenesis factors. DNA copy number variants (CNVs) were determined to compare the differences between the frequencies of GSTM1 and GSTT1 in a control group and patients. Then, the association of these genes with the pathological/survival status of HCC patients was investigated. Forty-nine Thai HCC patients' DNA and the genomic DNA of 66 healthy controls were investigated for GSTM1 and GSTT1 CNVs by real-time polymerase chain reaction (PCR). Then, the correlations between GSTM1 and GSTT1 patients' CNVs, the control group, and clinico-pathological parameters were determined. The results show that were no differences between the CNVs of GSTM1 and GSTT1 in the controls and patients (P≥0.05). Only GSTT1 genotypes 0/0 correlated to an increase in the risk of hepatocellular carcinogenesis (OR value was 1.88). GSTM1 CNVs were associated with the gender of patients (P=0.002). However, no correlations were found between GSTT1 CNVs and any of the clinico-pathological parameters. The results suggest that only GSTT1 CNVs are associated with increased risk factors of HCC in Thais. GSTM1 copy numbers had a dominant correlation with female HCC patients.

Glutathione S-transferase T1, M1 and P1 gene polymorphisms and susceptibility to colorectal cancer, a Syrian population study

Colorectal cancer (CRC) is considered to be the third most common cancer worldwide, and it is the fourth most common cause of cancer deaths. CRC is described as multifactorial disease. Among others, Glutathione S-transferases are known to act pro-carcinogenic in CRCs, however, they are needed for the conjugation between chemotherapeutics and a wide spectrum of xenobiotics. In this study, 70 patients with CRC and 85 healthy volunteers without any cancer history were genotyped. Polymorphism genotypes for the genes GSTP1, GSTT1 and GSTM1 were studied by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) and/or multiplex polymerase chain reaction. Our finding showed a significant risk for CRC associated with GSTP1 heterozygous Ile/Val (OR = 1.8; 95% CI: 0.93–3.44; p = 0.009), while GSTP1 Val/Val homozygous was observed only in the CRC patients. Significant differences in the frequency of GSTM1- and GSTT1-null genotypes were found. The GSTT1-null genotype was higher in CRC group (34.3%) than in control group (12.9%) (OR = 3.5; 95% CI: 1.57–7.83; p = 0.001). The GSTM1-null was higher in CRC cases (42.8%) compared with control group (21.1%) (OR = 2.79; 95% CI: 1.38–5.64; p = 0.003).Individuals carrying combined, both GSTM1/GSTT1-null genotype, were associated with an estimated 7.56-fold higher risk to form CRC than those having GSTM1/GSTT1-present genotype. Individuals carrying combined three genotypes of GSTM1-null/GSTT1-null/ heterozygous Ile/Val genotype for GSTP1 were associated with an estimated 21.63-fold higher risk to be CRC than those carrying GSTM1-present/GSTT1-present/ Ile/Ile genotype of the GSTP1 (OR = 21.63; 95% CI: 2.39–195.82; p = 0.001). Also, individuals with combined three genotypes of GSTM1-null/GSTT1-present/ heterozygous Ile/Val genotype for GSTP1 were associated with an estimated 13.9-fold higher risk to be CRC than those carrying GSTM1-present/GSTT1-present/ Ile/Ile genotype of the GSTP1 (OR = 13.9; 95% CI: 2.60–74.35; p = 0.0007). Overall, the results of this pilot study in 70 patients revealed that the GSTM1-null genotype, alone or in combination with GSTT1-null genotype, GSTP1-heterozygous is associated with enhanced risk for CRC in Syrian population.

Association of Genetic Polymorphism of GSTM1 and GSTT1 with the Susceptibility to Antituberculosis Drug-induced Hepatotoxicity in Chinese Population

Objective To investigate the relationship between the polymorphism of glutathione S transferase M1, T1(GSTM1, GSTT1) gene and the susceptibility to antituberculosis drug induced hepatotoxicity (ATDH) in patients with tuberculosis. Methods GSTM1 and GSTT1 gene polymorphisms in patients with or without liver toxicity after antituberculous treatment were analyzed using multiple PCR method. Results In ATDH group and control group, the proportion of GSTM1 gene deletion was 58.0% and 50.7%respectively, and the difference was not statistically signifcant (OR=1.322, 95%CI=0.921~1.878), the frequencies of GSTT1 deletion were 46.3% and 49.3%, respectively, and there was no signifcant difference between them. There was no signifcant difference in frequency of GSTM1 and GSTT1 variation between case group and control group (P&gt; 0.05), and no synergistic effect of those two gene polymorphism were detected in the occurrence of antituberculosis drug-induced hepatotoxicity. Conclusion The polymorphisms of GSTM1 and GSTT1 genes may not be associated with the risk of ATDH.

The diagnostic potential of glutathione S-transferase (GST) polymorphisms in patients with colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers in the world. Despite improvements in screening for early diagnosis, CRC is one of the leading causes of cancer deaths. The aim of the study was to determine a potential association between the frequency of GSTM1 and GSTT1 null genotypes and the risk of CRC in the Polish population. Moreover, we analyzed the clinical parameters with the glutathione S-transferase (GST) gene polymorphisms in patients with CRC. The study was conducted on 512 Caucasians, including 279 patients (105 women and 174 men) with CRC. DNA from peripheral blood was extracted and the multiplex polymerase chain reaction (PCR) technique was used for glutathione S-transferase theta (GSTT1) and mu (GSTM1) gene deletion genotyping. We found no statistically significant differences in the frequency of the GST gene polymorphisms in patients with CRC and controls. The prevalence of the GSTM1*0 variant in the test subjects was higher than in controls (45.9% vs 42.9%; p > 0.05). The frequency of the GSTT1*0 variant was also higher in patients with CRC compared to the control population (21.1% vs 18.9%; p > 0.05). In addition, the effect of the GSTM1 and GSTT1 polymorphisms on the incidence of CRC was also analyzed. There was a slight, but not statistically significant, increase of the risk of colon cancer for the GSTM1*0 and GSTT1*0 variants. Moreover, we examined the GST genotype due to the cancer TNM classification and the location of the primary tumor. Statistically significant differences in the distribution of the GSTT1*0 and GSTT1*1 genotypes in both the stage and the location of the primary tumor were observed. It is suggested that the GSTT1 polymorphism may have an impact on the severity of the tumor and its location.

Abstract 1223: Significance of GSTM1 and GSTT1 gene polymorphism to breast cancer susceptibility in Nigerian women

Abstract Human glutathione-S-transferases play a key role in the metabolism of drugs and environmental chemicals. There have been conflicting reports on the association of breast cancer susceptibility with null genotypes of glutathione-S-transferase (GST) classes of mu and theta (GSTM1 and GSTT1). However, this is the first report of the association of null genotypes of GSTs with breast cancer patients from Nigerian population. By multiplex PCR, we examined the null genotypes of GSTM1 and GSTT1 in relation to breast cancer risk in Nigerian women. The case-control study included 56 clinically diagnosed breast cancer patients and age-matched control participants. Odds ratio (OR) and 95% confidence interval (Cl) from conditional logistic regression model were used to estimate the association between GSTM1 and GSTT1 subtypes and breast cancer risk. The frequencies of GSTM1 and GSTT1 null genotypes in breast cancer (BC) patients differed from healthy controls (HC) (61% in BC vs. 39% in HC and 66% in BC vs. 34% in HC for GSTM1 and GSTT1 respectively). GSTM1 and GSTT1 null genotypes and their combinations were associated with increased breast cancer risk [OR = 3.06 (95% Cl 0.98-9.48)], [OR = 14.06 (95% Cl 3.02-70.6)] and [OR = 6.98 (95% Cl = 0.11-16.5)] respectively. The study showed an increased breast cancer risk in patients with GSTT1 homozygous gene deletions with relative risk (RR) value of 5.6 than those with GSTM1 (RR = 1.77). In conclusion, the data from our work provide evidence of increased risk of breast cancer associated with GSTM1 and GSTT1 homozygous gene deletions in women from Nigeria. Citation Format: Olubanke O. Ogunlana, Omaghomi Ortiseweyinmi, Sadiq Ajoke, Omolara Fatiregun, Solomon O. Rotimi, Bose E. Adegboye, Emeka E. Iweala, Angie O. Igbinoba-Adebayo. Significance of GSTM1 and GSTT1 gene polymorphism to breast cancer susceptibility in Nigerian women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1223.

Homozygous deletion of both GSTM1 and GSTT1 genes is associated with higher CD4+ T cell counts in Ghanaian HIV patients.

Glutathione S-transferase (GST) family of enzymes are involved in a two-stage detoxification process of a wide range of environmental toxins, carcinogens and xenobiotics. The GST enzymes play important roles in oxidative stress pathways, and polymorphisms in the GSTM1 and GSTT1 genes mediate susceptibility and outcome in different diseases. Human immunodeficiency virus (HIV) infection is associated with oxidative stress, but there is limited data on the frequency of deleted GSTM1 and GSTT1 genes in HIV/AIDS patients and their effect on progression among Ghanaians. This study sought to investigate the association between homozygous deletion of GSTM1 and GSTT1 genes (both null deletion) with HIV/AIDS disease progression in Ghanaian patients. HIV-infected individuals on antiretroviral therapy (ART), ART-naïve HIV patients, and HIV seronegative individuals were recruited for the study. HIV/AIDS disease progression was assessed by measuring CD4+ cell count and viral load of the patients, and GST polymorphism was determined by amplifying the GSTT1 and GSTM1 genes using multiplex PCR, with CYP1A1 gene as an internal control. The mean CD4+ count of patients that were naïve to ART (298 ± 243 cells/mm3) was significantly lower than that of patients on ART (604 ± 294 cells/mm3), and viral load was significantly lower in the ART-experienced group (30379 ± 15073 copies/mm3) compared to the ART-naïve group (209882 ± 75045 copies/mm3). Frequencies of GSTM1 and GSTT1 deletions were shown to be 21.9% and 19.8%, respectively, in the HIV patients, and patients with homozygous deletion of both GSTM1 and GSTT1 were more likely to have their CD4+ count rising above 350 cells/mm3 (OR = 6.44, 95% CI = 0.81–51.49, p = 0.039) suggesting that patients with homozygous deletion of GSTM1 and GSTT1 genes have slower disease progression. The findings of this study show that double deletion of glutathione S-transferases M1 and T1 is statistically associated with normal CD4+ count in patients diagnosed with HIV/AIDS. Further study is required to investigate the clinical importance of the both null deletion in HIV patients.

Investigation of Gluthatione S-Transferase Variants in a Healthy Population in Goiânia-Go

Genetic polymorphisms in glutathione S-transferases (GSTs) genes might influence the detoxification activities of the enzymes predisposing individuals to a lot of disiases. Owing to the presence of these genetic variants, inter-individual and ethnic differences in GSTs detoxification capacity have been observed in various populations. Therefore, the present study was performed to determine the prevalence GSTM1*0/*0, GSTT1*0/*0 and GSTP1 Ile105Val polymorphisms in 100 healthy individuals from Goiânia - GO. GSTM1 and GSTT1 polymorphisms were analyzed by a Multiplex-PCR approach, whereas GSTP1 polymorphisms were examined by PCR-RFLP. The frequencies of GSTM1 and GSTT1 *0/*0 genotypes are 49% and 31%, respectively. The frequencies of GSTP1 Ile/Ile, Ile/Val and Val/Val genotypes were 40%, 53% and 7%, respectively. The wild-type (Ile) and variant (Val) allele frequencies were 66.5% and 33.5%, respectively. The combined genotypes distribution of GSTM1, GSTT1 and GSTP1 polymorphisms showed 12 possible genotypes present in our population; seven of them have a frequency greater than 5%. The effect of combined genotypes of these GSTs polymorphisms is still unknown. These findings in healthy population, give us such more information for the future epidemiological and clinical studies. Using to examine the effect of these combinations in drugs metabolism and cancer predisposition, further largest group would be needed, since their frequencies are quite low. To our of GSTs polymorphisms, this is the first study indicating the frequencies of genetic polymorphisms of GST superfamily in a health population in a Goiania population.

Genetic Factors Associated with Risk and Disability Progression of Multiple Sclerosis in Slovak Population

Abstract Objective: The aim of our study was to determine the relation of particular genetic variants in selected genes (GSTM1, GSTT1 null genotypes; rs1695 GSTP1; rs10735781 EVI5) to the risk of multiple sclerosis (MS) development and find out the possible association with disease disability progression rate. Material and methods: Our study included 202 MS patients and 174 healthy control volunteers. MS patients were divided according to disability progression rate to three groups - slowly progressing, mid-rate progressing and rapidly progressing. All DNA samples were isolated from venous blood. Genotyping was performed by PCR-RFLP and multiplex PCR. Results: Our analysis showed that GSTT1 null genotype (OR 0.56; 95%CI 0.33 -0.95; p=0.04) and GSTM1, GSTT1 double null genotype (OR 0.32; 95%CI 0.14 - 0.74; p=0.006) are potentially protective in relation to MS. We observed similar result in GSTT1 null genotype in association with mid-rate progression (OR 0.48; 95%CI 0.24 - 0.97; p=0.05). Frequency of GSTM1 and GSTT1 double null genotype is significantly lower in subgroup of MS patients with progression rate defined as slow (OR 0.22; 95%CI 0.05 - 0.98; p=0.05) and middle (OR 0.33; 95%CI 0.11 - 0.99; p=0.045). We did not show any significant association of genetic changes rs1695 in GSTP1 and rs10735781 in EVI5 with MS or rate of disease progression. Conclusions: Genetic basis of multiple sclerosis is still not fully elucidated. Further research may clarify our results and confirm the value of studied factors for clinical practice.

АЛЕЛЬНИЙ ПОЛІМОРФІЗМ ГЕНІВ GSTS У МАТЕРІВ ІЗ ПЛАЦЕНТАРНОЮ ДИСФУНКЦІЄЮ ТА ЇХ НОВОНАРОДЖЕНИХ: АКУШЕРСЬКІ ТА ПЕРИНАТАЛЬНІ НАСЛІДКИ

Роль плаценти зумовлена реалізацією ряду функціональних механізмів забезпечення росту і внутрішньоутробного розвитку плода. Глутатіон-S-трансферази беруть активну участь у знешкодженні продуктів пероксидного окиснення ліпідів та пероксидів ДНК, відновлюючи органічні гідроперекиси в спирти та сприяючи ізомеризації деяких стероїдів та простагландинів. При наявності певних поліморфних варіантів GSTT1, GSTM1, GSTP1 генів сімейства глутатіон-S-трансфераз проходить виснаження глутатіонзалежного АОЗ та пригнічення детоксикаційної функції плаценти.Мета дослідження – визначити алельний поліморфізм генів глутатіон-S-трансфераз GSTT1 та GSTM1 у жінок із плацентарною дисфункцією, в здорових новонароджених та новонароджених із затримкою внутрішньоутробного розвитку на основе проведеного молекулярно-генетичного дослідження пуповинної крові.Матеріли і методи. У дослідження було залучено 105 жінок: основну групу склали 33 жінки з плацетарною дисфункцією (ПД) без затримки внутрішньоутробного розвитку (ЗВУР) у дітей, яких вони народили (перша група), та 17 жінок із ПД та ЗВУР (друга група). Контрольну групу склали 55 жінок (третя група), які народили здорових доношених дітей.Результати досліджень та їх обговорення. Встановлено, що ризик розвитку ПД та ПД зі ЗВУР за домінантної моделі успадкування (313AG + 313GG порівняно з 313AA) достовірно зростав. Перспективними прогностичними моделями міжгенної взаємодії для оцінки розвитку ПД передбачається аналіз варіантів генів GSTM1, GSTP1, а ПД зі ЗВУР – GSTT1, GSTM1, GSTP1. У результаті аналізу проб сироватки пуповинної крові та отриманих даних встановлено, що частота поліморфного варіанта GSTМ1“+” у всіх новонароджених області склала 42,69 %, а GSTМ1 “–” – 57,30 %. Частота поліморфного варіанта GSTT1“+” у всіх новонароджених області становила 79,77 %, а GSTT1 “–” – 20,22 %.Висновки. Результати досліджень розподілу різних алельних варіантів генів GSTM1 і GSTT1 показали їх відмінності у різних групах новонароджених. Виявлено вірогідну різницю між частотами делеційного варіанта гена GSTM1 у здорових новонароджених та новонароджених із ЗВУР. Сукупний аналіз комбінованого впливу декількох чинників виявив, що перебіг вагітності у жінок із ПД, гестозом та генотипом GSTМ1deletion асоціюється із значним зростанням ризику ЗВУР у плодів.

Association of glutathione S-transferase GSTM1 and GSTT1 deletion polymorphisms with obesity and their relationship with body mass index, lipoprotein and hypertension among young age Saudis.

ObjectivesPersistent oxidative stress is one of the several risk factors that may be associated with the etiology of obesity. The present study is aimed to investigate association between GSTM1 and GSTT1 polymorphisms with obesity and their relationship with plasma lipoproteins, body mass index (BMI) and hypertension.DesignThe GSTM1 and GSTT1 deletion polymorphisms were analyzed by multiplex polymerase chain reaction. The lipoproteins were measured in plasma using commercially available kit and the weight, height, systolic (SBP) and diastolic (DBP) blood pressures by standard procedure of measurements.SettingPrince Sultan Military Medical City, Riyadh Saudi Arabia.ParticipantsA total of 420 overweight/obese cases and 234 normal weight controls belong to young age Saudis.Main outcomes measuresGSTM1/GSTT1 polymorphisms may be associated with obesity.ResultsWeight, BMI, low-density lipoprotein (LDL) and SBP were significantly higher while high-density lipoprotein (HDL) was significantly lower in cases in comparison to controls. Frequency of GSTM1+/GSTT1− (OR = 2.70, 95% CI = 1.52–4.81, p = <0.001) and GSTM1−/GSTT1− (OR = 2.43, 95% CI = 1.15–5.15, p = 0.018) was significantly higher in cases as compared to controls. BMI and weight were significantly higher in GSTM1+/GSTT1− and GSTM1−/GSTT1− genotypes, and LDL, DBP and SBP significantly higher in GSTM1−/GSTT1− null genotype while HDL was significantly lower in GSTM1−/GSTT1+ and GSTM1−/GSTT1− genotypes in comparison to GSTM1+/GSTT1+ genotype.ConclusionsThe GSTM1+/GSTT1− and GSTM1−/GSTT1− null genotypes were significantly associated with obesity and have shown relationship with obesity risk factors in cases. Hence, these genes may be associative genetic risk factor for obesity among young age Saudis.

Polymorphisms of xenobiotic biotransformation genes and their role in individualization of pharmacological therapy and support of humans after heavy psychophysical loading

We analyzed the frequency distribution of CYP1A1, EPHX1, GSTM1, GSTP1, GSTT1 genes polymorphisms in 111 persons exposed to high physical and mental stress (elite athletes). Qualifications of sportsmen ranged from candidates for master of sports to world-class athlete. Comparative analysis revealed significant differences between the main group and the comparison group in the frequency of GSTM1, GSTT1, CYP1A1 genotypes, and a tendency to a predominance of genotype GSTP1 Val / Val in the main group.

Association of GSTM1, GSTT1, GSTP1-ILE105VAL and ACE I/D polymorphisms with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin. The aim of this study is to clarify the relationships between susceptibility and severity of AS and GST-mu1 (GSTM1), GST-theta1 (GSTT1), GST-pi1 (GSTP1)-Ile105Val and angiotensin-converting enzyme (ACE) I/D polymorphisms in AS patients. One hundred thirty-eight AS patients and seventy-one healthy controls were enrolled in this study. Erythrocyte sedimentation rate and C-reactive protein (CRP) levels of the AS patients were recorded. The scores of the numeric rating scale (NRS) pain, the Bath Ankylosing Spondylitis Activity Index, the Bath Ankylosing Spondylitis Metrology Index and the Bath Ankylosing Spondylitis Functional Index were calculated. The genotypes distributions and allele frequencies of GSTM1, GSTT1, GSTP1-Ile105Val and ACE I/D polymorphisms were compared between patients and healthy controls. The Multiplex polymerase chain reaction (PCR) and the PCR-restriction fragment length polymorphism methods were used to detect the polymorphisms of ACE I/D, the GSTT1 and GSTM1 genes and the GSTP1-Ile105Val polymorphism, respectively. There were significantly higher levels of the GSTT1 null and the ACE II genotypes in AS patients compared to those in healthy controls (p = 0.002 and 0.005, respectively). We found significantly higher levels of CRP and the NRS pain scores in the patients with ACE ID or DD genotypes compared to those in the patients with ACE II genotypes (p = 0.005 and 0.035, respectively). The present results showed that genes involved in protection from oxidative stress and ACE gene may influence disease development and course in AS.

Distributions of the GSTM1 and GSTT1 null genotypes worldwide are characterized by latitudinal clines.

Deletion types of genetic variants of glutathione S-transferase (GST) M1 and T1, the GSTM1 null and GSTT1 null which are risk factors for certain cancers, have been ubiquitously found in human populations but their worldwide distribution pattern is unclear. To perform a meta-analysis, a systematic search for the literature on GSTM1 and GSTT1 null genotypes was done to identify 63 reports for 81 human populations. Relationships between the GSTM1 and GSTT1 null genotype frequencies and the absolute latitude of 81 populations were tested by Spearman's rank correlation coefficient. A significant positive correlation was detected between the GSTM1 null genotype frequency and the absolute latitude (r=0.28, p-value <0.05), whereas the GSTT1 null genotype frequency and absolute latitude showed a significant negative correlation (r= -0.41 p-value <0.01). There was no correlation between the frequencies of GSTM1 and GSTT1 null genotype in each population (r= -0.029, p-value=0.80). Latitudinal clines of the distribution of the GSTM1 and GSTT1 null genotypes may be attributed to the result of gene-environmental adaptation. No functional compensation between GSTM1 and GSTT1 was suggested by the lack of correlation between the null frequencies for GSTM1 and GSTT1.

Polymorphisms in Glutathione S-Transferase M1, T1, and P1 in Patients with Chronic Periodontitis: A Pilot Study.

Background. Although the direct cause of chronic periodontitis is bacterial infection, the progression of this disease depends on genetic and environmental factors, and smoking is a known risk factor in the development and severity of the disease. An individual's susceptibility may be influenced by polymorphisms in the glutathione S-transferase genes. These genes encode enzymes that metabolize xenobiotic compounds. The aim of this study was to determine the frequency of GSTM1, GSTT1, and GSTP1 polymorphisms in Mexicans with chronic periodontitis. Methods. 60 Mexicans with chronic periodontitis (30 smokers and 30 nonsmokers) were studied. A peripheral blood sample was taken for subsequent DNA extraction. The genetic material was PCR-amplified followed by restriction fragment length polymorphism with the aim of identifying GST polymorphisms. Results. Polymorphisms in the GSTT1 and GSTP1 genes were not significantly different between the smokers and nonsmokers. However, there were significant differences (P = 0.05) between groups in polymorphisms in the GSTM1 gene. The patients with chronic periodontitis have a higher frequency of null and mutant polymorphisms in GSTM1, GSTT1, and GSTP1 compared with historical data from a healthy Mexican population. Conclusions. The presence of these polymorphisms may be a risk factor for the development of chronic periodontitis.