Relevance of glutathione S-transferase M1 and cytochrome P450 1A1 genetic polymorphisms to the development of head and neck cancers.

BACKGROUND: Cytochrome P450 (CYP) and glutathione S-transferase (GST) gene variants have been intensively investigated for their implication in the development of different neoplasms. METHODS: In the present study, we analyzed genetic polymorphisms of CYP1A1, GSTM1, GSTP1, and GSTT1 in 127 head and neck cancer patients and 151 hospital controls. RESULTS: No significant increase in risk in patients with the GSTM1 null genotype (OR=1.52, 95% CI: 0.93-2.49) or CYP1A1 462Val alleles (OR=1.60, 95% CI: 0.73-3.52) or GSTP1 105Val alleles (OR=0.97, 95% CI: 0.59-1.58) was observed. The GSTT1 null genotype was found in 30.5% of the controls and 21.3% of the head and neck cancer patients (p=0.15). The estimated head and neck cancer risk for the combination of either CYP1A1 Ile462Val or CYP1A1 Val462Val genotype with either GSTP1 Ile105Val or Val105Val genotype (OR=2.89, 95% CI: 0.71-11.71) and for the combination of either CYP1A1 Ile462Val or CYP1A1 Val462Val genotype with GSTT1 null genotype (OR=2.62, 95% CI: 0.64-10.85) suggested the absence of the modifying effect of combined variant alleles on head and neck cancer susceptibility. The joint effect of either CYP1A1 Ile462Val or CYP1A1 Val462Val genotype with GSTM1 null genotype significantly increased the risk of head and neck cancer (OR=7.15, 95% CI: 1.49-34.32). CONCLUSIONS: Our findings corroborate metabolic genes interactions, especially for CYP1A1 462Val alleles and GSTM1 homozygous deletion, in the development of head and neck cancer in the investigated population groups in Poland.     

The role of the glutathione S-transferase genes GSTT1, GSTM1, and GSTP1 in acetaminophen-poisoned patients

The aim of this study was to assess if genetic variants in the glutathione-S-transferase genes GST-T1, M1, and P1 reflect risk factors in acetaminophen (APAP)-poisoned patients assessed by investigation of the relation to prothrombin time (PT), which is a sensitive marker of survival in these patients. A total of 104 APAP-poisoned patients were genotyped for deletion polymorphisms in the GSTT1 and GSTM1 genes and for the GSTP1 Ile105Val polymorphism. We found a borderline association (p = 0.05) between the GSTT1 homozygous deletion genotype and high trough PT (a marker of prognosis in APAP poisoning) compared to carrying two functioning copies of the gene. No significant association was found between any of the GSTM1 and GSTP1 genotypes and PT. The frequency of GSTP1 Val/Val genotypes was significantly lower in the patients than in the background population (p = 0.047). The results suggest that the GSTT1 homozygous deletion genotype may be associated with a better prognosis after APAP poisoning and that carriers of the GSTP1 homozygous variant genotype may have a decreased risk of being APAP poisoned.     

Polymorphisms of cytochrome P450 1A1, glutathione S-transferase class mu, and tumour protein p53 genes and the risk of developing gallbladder cancer in Japanese

OBJECTIVES: To examine the relationship between genetic polymorphisms of cytochrome P450 1A1 (CYP1A1), glutathione S-transferase class mu (GSTM1), and tumour protein p53 (TP53) genes, and gallbladder cancer (GBC) risk, a case-control study was conducted. DESIGN AND METHODS: Genotypes of CYP1A1 T3801C, CYP1A1 Ile462Val, GSTM1, and TP53 Arg72Pro were determined in 54 cases of GBC and 178 controls. RESULTS: The age-adjusted odds ratios (ORs) for the Ile/Val genotype of CYP1A1 Ile462Val polymorphism in women and the Arg/Pro genotype of TP53 Arg72Pro polymorphism in men were observed to be 2.70 (95% CI: 1.14-6.40) and 4.32 (95% CI: 1.08-17.2), respectively. No significant differences in the genotypic frequencies of CYP1A1 T3801C and GSTM1 polymorphisms were observed between controls and cases in both men and women. CONCLUSION: These results suggest that the Val allele of CYP1A1 Ile462Val polymorphism and the Pro allele of TP53 Arg72Pro polymorphism contribute to an increased risk of GBC among Japanese women and men, respectively.     

Pharmacokinetics and toxicity of docetaxel: role of CYP3A, MDR1, and GST polymorphisms

OBJECTIVE: Patients initiating docetaxel chemotherapy were genotyped for CYP3A4, CYP3A5, MDR1, GSTM1, GSTT1, GSTM3, and GSTP1 to identify variability factors of docetaxel pharmacokinetics and toxicity. METHODS: Genotyping was performed by direct sequencing (CYP3A4), real-time polymerase chain reaction (CYP3A5), and polymerase chain reaction-restriction fragment length polymorphism (MDR1 and GST). The clearance and area under the curve of docetaxel were calculated by use of a Bayesian approach. Absolute neutrophil count was recorded twice weekly. RESULTS: With regard to the pharmacokinetic analysis, 58 patients were included. CYP3A4*1B carriers (*1A/*1B, n=4), who are also CYP3A5*1/*3 carriers, had a significantly higher clearance and lower dose-normalized area under the curve of docetaxel than those with the wild genotype (*1A/*1A, n=53): 55.2+/-13.5 L/h versus 37.3+/-11.7 L/h (P=.01) and 31.4+/-6.2 (microg . h/L)/(mg/m(2)) versus 52.7+/-18.2 (microg . h/L)/(mg/m(2)) (P=.005), respectively. No influence of MDR1 was evidenced. With regard to the pharmacodynamic analysis, febrile neutropenia occurred more frequently in GSTP1*A/*B carriers (31.6% versus 3.7% in *A/*A carriers and 0% in *A/*C, *B/*B, and *B/*C carriers) (P=.037). Grade 3 neutropenia occurred more frequently in 3435TT MDR1 genotype carriers: TT, 100%; CT, 77.3%; and CC, 54.5% (P=.046). No influence of GSTM1, GSTT1, or GSTM3 polymorphisms was evidenced on docetaxel toxicity. CONCLUSIONS: Patients carrying the CYP3A*1B allele may have enhanced docetaxel clearance and may be underexposed, whereas those carrying GSTP1*A/*B and 3435TT genotypes may have excessive hematologic toxicity. Further studies are warranted to determine the usefulness of genotyping before docetaxel treatment.     

Polymorphisms of glutathione S-transferase M1, T1, and P1 in patients with HBV-related liver cirrhosis, chronic hepatitis, and normal carriers

OBJECTIVES: Persistent hepatitis B virus (HBV) infection often leads to the development of chronic hepatitis and cirrhosis. The role of host genetic factors in chronic HBV infection is not fully understood. We studied the influence of glutathione S-transferase (GST) M1, T1, and P1 polymorphisms in patients with different stages of HBV infections. METHODS: The sample population included 41 HBV normal carriers, 37 patients with chronic hepatitis, and 38 patients with cirrhosis (infected with HBV) compared to a control group (n = 59). PCR-based procedures were performed in the studied populations to confirm the genotypes of GSTT1, M1, and P1. Odds ratio analysis tests were used for statistical evaluation. RESULTS: We found that the frequency of GSTP1-Val (105)/Val (105) genotype was significantly higher in patients with liver cirrhosis (27%) than HBV normal carriers (2.4%; OR 14.8, 95% CI 1.8-122.5) and the frequency GSTP1-Val (105)/Ile (105) genotype was significantly higher in patients with liver cirrhosis (59.5%) than HBV normal carriers (19.5%; OR 6.1, 95% CI 2.1-16.7). The genotype GSTP1-Val (105)/Val (105) was more frequent in patients with chronic hepatitis (19.4%) than HBV normal carriers (2.4%; OR 9.65, 95% CI 1.1-82.8). Patients with cirrhosis also had a higher frequency of the GSTM1 null genotype (71.1%) than HBV normal carriers (27.5%; OR 6.5, 95% CI 2.4-17.4) and the GSTM1 null genotype was more frequent in patients with chronic hepatitis (64.9%) than HBV normal carriers (27.5%OR 4.9, 95% CI 1.8-12.8). The frequency of GSTT1 genotype was similar in all groups. CONCLUSION: These results suggest that in HBV infection, inheritance of the null GSTM1 and GSTP1-Val (105) polymorphisms involves a host genetic factor that is relevant to disease progression.     

Multiplex PCR detection of GSTM1, GSTT1, and GSTP1 gene variants: simultaneously detecting GSTM1 and GSTT1 gene copy number and the allelic status of the GSTP1 Ile105Val genetic variant

The glutathione S-transferase (GST) genes GSTM1, GSTT1, and GSTP1 are involved in the detoxification of a broad range of toxic substances. Genetic polymorphisms in these genes have been studied intensively for their potential role in cancer susceptibility and drug response. In Caucasians, the enzyme activity of GSTM1 and GSTT1 is absent in approximately 50 and 15% of the population, respectively, due to deletions of both chromosomal copies of the genes. A trimodal phenotype pattern exists in which individuals with two, one, or no functional genes are fast, intermediate, or slow "conjugators," respectively. Most studies investigating the effect of the GSTM1 and GSTT1 deletions do not distinguish between fast and intermediate conjugators because the applied genotyping assays only detect if at least one copy of either gene is present. We present a multiplex PCR assay that detects if an individual has none, one, or two copies of the GSTM1 and GSTT1 genes and simultaneously detects the allelic status of the GSTP1 Ile105Val genetic variant. A total of 200 Danes, 100 Somalis, and 100 Greenlanders were genotyped. This multiplex PCR assay enables future large-scale studies to investigate the role of GSTs.     

Glutathione S-transferase P1 *C allelic variant increases susceptibility for late-onset Alzheimer disease: association study and relationship with apolipoprotein E epsilon4 allele

BACKGROUND: Oxidative stress and neuronal cell death have been implicated in the pathogenesis of Alzheimer disease (AD). Considering that the glutathione transferase (GST) supergene family encodes isoenzymes that appear to be critical in protection against oxidative stress, we aimed at determining the various GSTP1, GSTM1, and GSTT1 polymorphisms and ApoE genotypes to investigate their role as susceptibility genes for late-onset AD (LOAD). METHODS: We included 210 LOAD patients and 228 healthy controls matched for age, sex, and educational level in our case-control genetic association study. GSTM1 and GSTT1 genotypes were studied by conventional PCR, whereas GSTP1 and ApoE genotypes were determined by real-time PCR on the LightCycler. RESULTS: We found a significant association between LOAD and the GSTP1*C allelic variant [odds ratio (OR) = 1.9; P < 0.05], but no association between the GSTM1 and GSTT1 deleted genotypes and LOAD. In addition, a preliminary result suggested that carriers of both the GSTP1*C and ApoE epsilon4 allelic variants were at increased risk of LOAD (OR = 19.98; P < 0.0001). CONCLUSION: The GSTP1*C allelic variant should be considered a candidate for LOAD, particularly in persons having the ApoE epsilon4 allelic variant, because the GSTP1 and ApoE gene products are implicated in oxidative stress and apoptosis processes leading to beta-amyloid-mediated neurodegeneration.     

Frequency of -163 C>A and 63 C>G single nucleotide polymorphism of cytochrome P450 1A2 in two African populations.

Cytochrome P450 1A2 (CYP1A2) is an important member of the cytochrome P450 superfamily of enzymes because of its involvement in the metabolism of some carcinogens and therapeutically important drugs. As a result, factors affecting the activity of the enzyme are the focus of considerable research effort as they may have important pharmacological or toxicological implications. CYP1A2 has been shown to exhibit a genetic polymorphism with most of the data, however, coming from studies in Caucasian and Oriental populations. In this study therefore, we investigated the frequencies of two point mutations, -163C>A and 63C>G, in two Bantu African populations. A total of 214 healthy subjects were recruited from Zimbabwe (n=143) and Tanzania (n=71). The two single nucleotide polymorphisms were detected using polymerase chain reaction-restriction fragment length polymorphism analysis. The frequency of -163A was 57% (95% confidence interval (CI), 54%, 60%) and 49% (95% CI, 45%, 53%) among Zimbabweans and Tanzanians, respectively, but the difference between the two populations was not statistically significant (p=0.123). The base change 63 C>G was not found in any of the subjects from the two populations. We report here a high frequency of -163 C>A base change and an absence of the 63 C>G change in the two African populations.     

GSTM1-null and GSTT1-null genotypes are associated with essential arterial hypertension in patients with type 2 diabetes

ObjectiveTo evaluate whether the genetic polymorphisms of glutathione S-transferases M1 (GSTM1) and T1 (GSTT1), Ile105Val of the GSTP1 (rs947894), and the Val16Ala polymorphism of the MnSOD (rs4880) are associated with essential arterial hypertension (EAH) in Caucasians with type 2 diabetes.Design and methods1015 Slovenian subjects (Caucasians) with type 2 diabetes with/without EAH were enrolled in the cross-sectional study. Genotypes were determined by multiplex PCR amplification and PCR-restriction fragment length polymorphism method.ResultsIn the cross-sectional study, GSTM1-null genotype and GSTT1-null genotype were associated with EAH in subjects with type 2 diabetes (59.0% vs. 50.3%, p = 0.007; 28.5% vs. 20.7%, p = 0.008; consequently).ConclusionAfter adjustment for age, body mass index, and hsCRP level, GSTM1-null and GSTT1-null genotypes were found to be independent risk factors for the development of EAH in Slovenian patients with type 2 diabetes.     

谷胱甘肽巯基转移酶基因多态性在原发性肝细胞癌人群中的研究

目的探讨原发性肝细胞癌人群中谷胱甘肽巯基转移酶基因多态性与肝癌发生、发展的关系。方法我院2008年10月-2010年4月收治的原发性肝癌患者与健康体检者各150名,提取血样,利用多重PCR和限制性片段长度多态性检测法分别检测肝癌人群与体检健康者的谷胱甘肽巯基转移酶基因多态性,并进行对比分析。结果该肝癌人群中:谷胱甘肽巯基转移酶基因多态性型别在病例和对照组研究对象中出现的频率无显著性差别,P>0.05;GSTM1-null、GSTT1-null、GST01-Ala140Asp、GSTP1-Ile105Val的多态性情况与该地区已有的报道一致。结论谷胱甘肽巯基转移酶基因多态性与肝癌的发生、发展无明确的相关关系。     

Rapid determination of common mutations in glutathione S-transferase gene by PCR-based methods in healthy Chinese

BACKGROUND: The glutathione S-transferase (GST) superfamily comprises multiple isozymes with compelling evidence of functional polymorphisms in various ethnic groups. All these mutations, in particular those in class mu, pi and theta GST, are likely to contribute to interindividual differences in responses to xenobiotics including response to chemotherapy and associated with altered disease. The frequency of common GST mutations in Uygur Chinese is unknown. We investigated the common mutations of GSTM1, GSTT1, and GSTP1 in Uygur (N=154) Chinese and compare with Han Chinese (N=196). METHOD: GSTM1 and GSTT1 polymorphisms were analyzed by multiplexed PCR, and GSTP1 polymorphism was detected by PCR-based restriction fragment length polymorphism (RFLP) analysis. RESULTS: GSTM1 null genotype was found in 53.2% Uygur Chinese, which was close to that in Han Chinese (56.1%) (P=0.592). A significantly lower frequency (P<0.05) of GSTT1 null genotype in Uygur Chinese (26.6%) was observed compared with Han Chinese (50.0%). Uygur Chinese exhibited a GSTP1 genotype distribution of 51.3% I/I, 40.2% I/V and 8.4% V/V, which was different from that in Han Chinese (60.7% I/I, 35.2% I/V and 4.1% V/V). CONCLUSIONS: There is marked ethnic difference in the frequency of common GSTT1 and GSTP1 mutation, but not GSTM1 mutation, between Uygur and Han Chinese.     

达斡尔族谷胱甘肽S-转移酶GSTT1和GSTM1基因多态性

目的探讨内蒙古地区达斡尔族谷胱甘肽争转移酶（glutathione S-transferases，GSTs）GSTM1和GSTT1基因多态性分布特点，为内蒙古少数民族基因型研究提供相关数据。方法采用内对照聚合酶链反应技术（PCR）和凝胶成像分析方法，对220例内蒙古地区达斡尔族个体的GSTT1、GSTM1基因缺失型频率进行了分析。结果GSTM1基因缺失型、GSTT1缺失型在内蒙古地区达斡尔族人群中检出频率分别为50．8％和71．4％。同时具有GSTM1缺失型和TSTT1缺失型个体的检出频率为31．4％。结论中国达斡尔族人群GSTM1、GSTT1基因呈多态性分布，与汉旅相比存在一定差异，与蒙古族相比差异无统计学意义。     

Cytochrome P450 2D6 and glutathione S-transferase M1 genotypes and migraine

BACKGROUND: Migraine is thought to be a disease of the brain and trigeminovascular system. Migraine patients often claim that stress, food, and beverages trigger their attacks. Chemical substances in these foodstuffs with the property of triggering migraine attacks have not yet been characterised. Cytochrome P450 2D6 (CYP2D6) and glutathione S-transferase M1 (GSTM1) are thought to be present in the brain. They metabolise numerous environmental compounds. The genes exhibit genetic polymorphism that is associated with altered enzyme activity. The aim of this study was to determine if the genotypes of these two enzymes are associated with migraine. MATERIALS AND METHODS: The study included 100 female patients and 245 female controls from the general population. Genomic DNA was isolated from whole blood. Allele specific PCR methods were used to identify the normal CYP2D6*1 allele and the mutated CYP2D6*3 and CYP2D6*4 alleles. Initially all samples were genotyped only for GSTM1 plus (+) and GSTM1 null (-) variants. All samples positive for GSTM1 were further analysed for the presence of allelic variants GSTM1*A and GSTM1*B. RESULTS: None of the CYP2D6 and GSTM1 genotypes was associated with migraine. We observed an odds ratio (OR) for the poor metaboliser genotype of CYP2D6 of 1.4 (95% CI = 0.5-3.6) and for the GSTM1 null genotype of 1.0 (95% CI = 0.6-1.5). CONCLUSION: The results of this study indicate that deficient metabolism because of mutated CYP2D6 alleles or GSTM1 allele variants is not important in the aetiology of migraine.     

Genetic polymorphism of GSTT1 and GSTM1 and susceptibility to chronic obstructive pulmonary disease (COPD)

Background

Chronic obstructive pulmonary disease (COPD) represents a major public health care problem worldwide due to its increasing prevalence, morbidity and mortality. Chronic obstructive pulmonary disease is known to be the fourth leading cause of death and the only cause of death, which is increasing. It is generally accepted that cigarette smoking is the most important risk factor for COPD. Nevertheless, only 10% to 20% of chronic smokers develop the severe impairment of pulmonary functions associated with COPD. This indicates the presence of genetic predisposing factors in its pathogenesis.

Objective

To test the hypothesis that genetic polymorphism of glutathione S-transferase θ 1 (GSTT1)and/or glutathione S-transferase μ 1 (GSTM1) is associated with COPD in smokers.

Materials and Methods

A case-control study was done on 34 patients with COPD and 34 matched controls. DNA was extracted from white blood cells by salting out method. GSTT1 and GSTM1 genotypes were amplified by polymerase chain reaction. The fragments were then analyzed by agarose gel electrophoresis. Statistical analysis was done using SPSS program.

Results

The frequency of carriers of null GSTT1 genotype was 50% among cases compared to 44.1% in the control group. Carriers of null GSTT1 were at minor risk of developing COPD when compared with carriers of the wild GSTT1 genotype (OR, 1.3; 95% CI, 0.5-3.3). In case of GSTM1, the frequency of carriers of null GSTM1 genotype was 52.9% among cases compared to 26.5% in controls. Carriers of null GSTM1 were at much higher risk of developing COPD (OR, 3.13; 95% CI, 1.1-8.6). Furthermore, the risk of developing COPD was increased among carrier of null GSTT1 &; GSTM1 haplotype (OR, 3.6; 95% CI, 1.1-11.6).

Conclusion

Carriers of null GSTM1 genotype were at high risk of developing COPD especially when they were null GSTT1 and GSTM1 haplotype.     

GSTT1 and GSTM1 gene deletions are not associated with hepatotoxicity caused by antitubercular drugs

Background and objective: Susceptibility to antitubercular drug (ATD)‐induced hepatotoxicity may be genetically mediated, with variant alleles of genes such as N‐acetyltransferase (NAT2) and CYP2E1 reported as risk factors. Two studies of Asian populations have reported that GSTM1*0/*0 (null) genotype was a likely predictor of hepatotoxicity, whereas another of a Caucasian population implicated GSTT1*0/*0. We undertook a prospective case–control study to investigate whether GSTM*0/*0 and GSTT1*0/*0 were risk factors for ATD‐induced hepatotoxicity. Methods: Pulmonary tuberculosis patients on isoniazid, rifampicin and pyrazinamide who developed hepatotoxicity using defined criteria were prospectively identified. These cases were then matched with at least one control subject on the same drugs but without hepatotoxicity. Genotyping for GSTM1 and GSTT1 was performed by multiplex PCR on genomic DNA. The odds ratios for the frequency of specific GSTM1 and GSTT1 homozygotes in the case and control subjects were calculated to test for association between the genotypes and hepatotoxicity. Results and discussion: Hundred and fifty‐one subjects (51 cases, 100 controls) were enrolled. Odds ratio for GSTM1 null genotype was 1·00 (95% CI 0·51–1·97) and GSTT1 null was 2·02 (95% CI 0·39–10·39), respectively, showing that these genotypes are not associated with hepatotoxicity. Conclusion: GSTM1 *0/*0 or GSTT1 *0/*0 or both null genotypes, do not appear to be associated with ATD‐induced hepatotoxicity in our Indian population.     

CYP3A4*1B and NAT2*14 alleles in a native African population.

Single nucleotide polymorphisms were examined in the cytochrome 450 3A4 (CYP3A4) and N-acetyltransferase 2 (NAT2) genes, which code for major mediators of the metabolism of a wide variety of therapeutic drugs, as well as xenobiotics. We determined, in a population from Guinea-Bissau, the frequencies of CYP3A4 and NAT2 variants expected to be prevalent among Africans, due to the high frequency previously observed in African Americans. The observed frequencies were 72% for CYP3A4*1B and 19.2% for the NAT2 191 G>A variant. The high frequency found for these potentially function-altering polymorphisms suggests the possibility of impaired metabolism through CYP3A4 and NAT2 in this population. Strikingly, the frequency observed for the NAT2 191 G>A single nucleotide polymorphism (SNP), associated with the slow acetylator phenotype, was significantly higher than found in other African populations, suggesting the existence of a west to east gradient across Sub-Saharan Africa. The prevalence of these variants may be relevant with regard to therapeutic efficacy in African populations for it may potentially affect drug clearance and consequently, increase the incidence of side effects and drug-drug interactions.     

Polymorphisms in genes involved in DNA repair and metabolism of xenobiotics in individual susceptibility to sporadic diffuse gastric cancer.

BACKGROUND: Gastric cancer is the second highest cause of cancer mortality in the world, despite declining rates of incidence in many industrialized countries. We carried out a case-control study to evaluate whether polymorphisms of DNA repair and glutathione S-transferase (GST) genes modulate the risk of developing diffuse gastric cancer. METHODS: ERCC1 118 T/C, XRCC1 399 G/A, XPD 312 G/A, XPD 751 A/C, XRCC3 241 C/T, MS 919 A/G, GSTP1 105 A/G, GSTM1-null/positive and GSTT1-null/positive genotypes were obtained for a series of 126 Helicobacter pylori-negative diffuse gastric cancer patients and 144 Helicobacter pylori-negative controls sampled from the population of Marche, an area with high gastric cancer risk in central Italy. RESULTS: GSTP1 105 A/G and GSTP1 105 G/G genotypes were identified as protective factors, with odds ratio (OR) of 0.4 (95% CI 0.17-0.81, p=0.01) and OR=0.58 (95% CI 0.33-1, p=0.05), respectively. GSTT1-null genotype was identified as a protective factor, with OR=0.48 (95% CI 0.22-0.99, p=0.04). There was no significant difference between cases and controls for XPD 751 A/C, ERCC1 118 T/C, XRCC3 241 C/T, XRCC1 399 G/A, XPD 312 G/A, GSTM1-null/positive and MS 919 A/G polymorphisms. CONCLUSIONS: This study suggests that GSTP1 105A/G and GSTT1-null/positive genotypes might be associated with a reduced risk for sporadic diffuse gastric cancer. Clin Chem Lab Med 2007;45:822-8.     

Association of GSTT1, GSTM1 and CYP1A1 polymorphisms with susceptibility to systemic lupus erythematosus in the Chinese population

BackgroundGSTT1, GSTM1, CYP1A1 are enzymes responsible for the detoxification of the toxicant which may be involved in the development of systemic lupus erythematosus (SLE). We examined the relationship between the risk of SLE and the polymorphisms of these genes in the Chinese population.MethodsSamples from 298 SLE patients and 284 healthy controls were collected. Polymerase chain reaction-restriction fragments length polymorphism (PCR–RFLP) was used to analyze the genotypes of CYP1A1 m2 and m4, while multiplex PCR was used to analyze the genotypes of GSTT1 and GSTM1.ResultsStatistically significant difference was observed in genotypes for GSTM1 (p = 0.003, OR 1.66 [95% CI 1.19–2.32]), but not for GSTT1 (p = 0.119, OR 0.77 [95% CI 0.56–1.07]), in the SLE patients as compared with the controls. Combinational analysis for double-null deletion of both GSTT1 and GSTM1 showed no significant difference (p = 0.863, OR 1.03 [95% CI 0.70–1.52]). Significant difference was observed in the genotype frequencies (p = 0.013), but not in the allele frequencies (p = 0.444, OR 0.90 [95% CI 0.70–1.17]), of CYP1A1 m2. All candidates have a wild-type genotype for CYP1A1 m4.ConclusionsPolymorphisms of GSTM1 are associated with SLE in the Chinese population.     

谷胱甘肽S-转移酶P1～105基因多态性与高原环境下人体运动能力的关系

背景:谷胱甘肽S-转移酶具有清除活性氧、提高机体抗氧化能力的作用.目的:分析谷胱甘肽S-转移酶P1～105基因多态性与高原环境下人体运动能力的关联性.设计、时间及地点:对照比较分析,于2007年在解放军体育进修学院完成.对象:实验组86名高原登山运动员为在高原环境下具有较强的作业能力的特定人群,对照组为解放军体育学院随机选取的90名健康学员.方法:采集86名高原登山运动员及90名健康学员的血样,提取基因组DNA,采用PCR-RFLP技术检测谷胱甘肽S-转移酶P1～105基因多态性,分别比较高原登山运动员与平原汉族对照人群间谷胱甘肽S-转移酶P1～105等位基因和基因型的分布.主要观察指标:谷胱甘肽S-转移酶P1～105基因型的分布.结果:共检测到谷胱甘肽S转移酶P1～105基因3种基因型:变异杂合型(A/G)、变异纯合型(G/G)、野生基因型(A/A).实验组谷胱甘肽S-转移酶P1～105的G等位基因、变异基因型(A/G+G/G)的频率皆明显低于对照组(P＜0.01).以变异基因型作为暴露因素,求得OR=2.19,95%CI=1.16～4.13,提示在高原环境下,与具有谷胱甘肽S-转移酶P1～105野生基因型人的运功能力比较,具有谷胱甘肽S-转移酶P1～105变异基因型人的运动能力下降了1.19倍.结论:谷胱甘肽S-转移酶P1～105基因多态性与高原环境下人体运动能力相关,野生基因型表现出明显的运动优势.