Polymorphism of glutathione S-transferases M1 and T1 in several populations of Russia

Frequencies of the wild-type and null genotypes of the GSTM1 and GSTT1 genes were established in healthy donors from several Russian populations (ethnic Russians from the towns of Oshevensk and Kholmogory, Arkhangel'sk oblast; ethnic Khants; ethnic Kalmyks; and ethnic Buryats) in order to identify the ethnic group with the maximal frequency of the null genotype. The highest frequency of individuals with the null genotype of both genes was observed in the Kalmyk and Buryat populations. The results may be used to study the effect of climatic and ecological conditions on multifactorial disease incidence in populations.     

Glutathione S-transferase M1 and T1 polymorphisms in Brazilian African descendants

The glutathione S-transferase gene family has an important role in the biotransformation and detoxification of different xenobiotics and endogenous compounds. Two polymorphic genes of this family, GSTM1 and GSTT1, present null alleles that consequently do not produce the respective enzyme when the genotype is homozygous. These polymorphisms are also interesting for population dynamics studies because they have great frequency variations among different ethnic groups and have been reported worldwide. The distribution of these alleles in urban and Amerindian populations in Brazil has been described, but none of those studies reported on African-descended rural populations. The aim of this study was to analyze the genotype frequency distribution of the GSTM1 and GSTT1 null alleles in an urban sample from the Federal District (n = 91) and in four semi-isolated African-descended populations: Mocambo (n = 55), Rio das R?s (n = 117), Riacho de Sacutiaba (n = 34), and Kalunga (n = 68). The GSTM1 and GSTT1 null genotype frequencies in these populations range from 17% to 35% for GSTM1 and from 22% to 44% for GSTT1. These values are similar to those described in other African and African-descended populations. Despite this range, there is no distribution difference among the analyzed populations. Combined GSTM1 and GSTT1 null genotype frequencies range from 6% to 13% and are similar to European-derived populations, suggesting admixture with this ethnic group. This can be interpreted as a European contribution to these African-descended populations. Regarding the urban population in the Federal District, our results suggest an important African and European contribution.     

Genotype frequencies of polymorphic GSTM1, GSTT1, and cytochrome P450 CYP1A1 in Mexicans

The genotype frequencies of three metabolic polymorphisms were determined in a sample of a typical community in central Mexico. CYP1A1*3, GSTM1, and GSTT1 polymorphisms were studied in 150 donors born in Mexico and with Mexican ascendants; with respect to ethnicity the subjects can be considered Mestizos. PCR reactions were used to amplify specific fragments of the selected genes from genomic DNA. An unexpected 56.7% frequency of the CYP1A1*3 allele (which depends on the presence of a Val residue in the 462 position of the enzyme, instead of Ile) was found, the highest described for open populations of different ethnic origins (i.e., Caucasian, Asian, African, or African American). The GSTM1 null genotype was found with a frequency of 42.6%, which is not different from other ethnicities, whereas the GSTT1 null genotype had a frequency of 9.3%, one of the lowest described for any ethnic group but comparable to the frequency found in India (9.7%). The frequency of the combined genotype CYP1A1*3/*3 and the GSTM1 null allele is one of the highest observed to date (or perhaps the highest): 13.7% among all the ethnicities studied, including Caucasians and Asians, whereas the combination of CYP1A1*3/*3 with the GSTT1 null allele reached only 2.8%. The GSTM1 null allele combined with the GSTT1 null allele, on the other hand, has one of the lowest frequencies described, 4.24%, comparable to the frequencies found in African Americans and Indians. Finally, the combined CYP1A1*3/*3, GSTM1 null allele, and GSTT1 null allele genotype could not be found in the sample studied; it is assumed that the frequency of carriers of these combined genotypes is less than 1%. CYP1A1*3 and CYP1A1*2 polymorphisms were also evaluated in 50 residents in a community of northern Mexico; the CYP1A1*3 frequency was 54%, similar to that found in the other community studied, and the CYP1A1*2 frequency was 40%, which is high compared to Caucasians and Asians but comparable to the frequency found in Japanese and lower than the frequency found in Mapuche Indians. Haplotype frequencies for these CYP1A1 polymorphisms were estimated, and a linkage disequilibrium value (D) of 0.137 was calculated.     

Genetic polymorphisms of glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) in selected populations of Afghanistan

Genetic polymorphisms in genes encoding glutathione S-transferase T1 (GSTT1, a member of class theta) and M1 (GSTM1, a member of class mu) have been defined. Previous studies have revealed that there was significant difference between populations for allelic frequency of several members of GSTs. In order to find the prevalence of null genotypes of GSTM1 and GSTT1 in Afghanis populations the present study was carried out. The total study subjects consisted of 656 unrelated healthy Afghanis refugees living in Fars province (southern Iran). From these 257, 217, 120, and 62 individuals were Pashtuns, Tajiks, Hazaras, and Uzbeks, respectively. Genetic polymorphisms for GSTT1 and GSTM1 were detected by multiplex PCR. The prevalence of null genotype of GSTM1 in Pashtuns, Tajiks, Hazaras, and Uzbeks was 42.4, 48.4, 52.5, and 40.3 %, respectively. There was no significant difference between these populations for the genotypic distribution of the GSTM1 polymorphism (χ(2) = 4.67, df = 3, P = 0.197). The frequency of GSTT1 null genotype in Pashtuns, Tajiks, Hazaras, and Uzbeks was 7.4, 25.3, 25.0, and 29.0 %, respectively. The observed difference between populations for prevalence of GSTT1 null genotype was statistically significant (χ(2) = 35.54, df = 3, P < 0.001). In comparison with European and Asian populations, Afghanistan populations like Iranian populations showed intermediate frequency for GSTT1 and GSTM1 null genotypes.     

Polymorphisms of CYP1a1, CYP2e1, GSTM1, GSTT1, and TP53 genes in Amerindians

Polymorphisms at the TP53, cytochrome P‐450 (CYP), and glutathione S‐transferase (GST) genes are related to cancer susceptibility and present high diversity in allele frequencies among ethnic groups. This study concerns the CYP2E1, GSTM1, and GSTT1 polymorphisms in seven Amerindian populations (Xavante, Guarani, Aché, Wai Wai, Zoró, Surui, and Gavião). Polymorphic sites at CYP1A1 and TP53 were also studied in the Aché and Guarani tribes and compared with previous results about these systems already obtained in the other populations. The CYP2E1*5B haplotype showed, respectively, the highest and the lowest frequencies already observed in human groups. High frequencies of CYP1A1*2A and CYP1A1*2C alleles and mostly low values of GSTM1*0/*0 and GSTT1*0/*0 genotypes were observed. These data may be interpreted as being due to genetic drift or selection for these high‐frequency CYP1A1 alleles and against GST null genotypes during America's colonization. Intrapopulation diversity varied from 0.19 (Guarani) to 0.38 (Surui), and 90% of the total diversity was due to the variability within populations. The relationships between these Amerindians and with other ethnic groups were evaluated based on D_A distances and the neighbor‐joining method. Low correlation was observed between genetic relationships and geographic distances or linguistic groups. In the TP53 comparison with other ethnic groups, Amerindians clustered together and then joined Chinese populations. The cluster analysis seems to indicate that the Aché tribe might descend from a Gê group that could have first colonized that Paraguayan region, but had also assimilated some amount of the Guarani gene pool, maybe through intertribal admixture. Am J Phys Anthropol 119:249–256, 2002. © 2002 Wiley‐Liss, Inc.     

Glutathione <Emphasis Type="BoldItalic">S</Emphasis>-transferase M1 and T1 null genotype frequency distribution among four tribal populations of western India

Glutathione S-transferase (GST) family is a key contributor in the detoxification mechanism of our body. Deletion of the genes within this family has been reported in the failure of detoxification system, to some extent leading to various types of cancers and other life threatening diseases. The existing data and reports on the association of null genotype of both GSTM1 and GSTT1 genes for various diseases are inconsistent. But knowledge of the polymorphic distributions of genotypes in different populations is important for investigating the risk factors in different epidemiological studies. The present study thus aims to determine the frequency of GSTM1 and GSTT1 null genotype frequency among four tribal groups, i.e. Mina, Garasia, Damor and Saharia of western India. A comparative analysis with different tribal as well as world population has also been undertaken to have a view of its worldwide frequency distribution. Our results reveal a frequency distribution varying from 22.6% to 66.9% with respect to GSTM1 gene polymorphism and from 19.1% to 33.0% with respect to GSTT1 gene in the studied populations. To the best of our knowledge this is the first report on the GSTM1 and GSTT1 frequency distribution among the tribal population of western India and our study shows that the Mina tribal population has the highest frequency of GSTM1.     

Estimation and adjustment of microsatellite null alleles in nonequilibrium populations

Nonamplified (null) alleles are a common feature of microsatellite genotyping and can bias estimates of allele and genotype frequencies, thereby hindering population genetic analyses. The frequency of microsatellite null alleles in diploid populations can be estimated for populations that are in Hardy–Weinberg equilibrium. However, many microsatellite data sets are from nonequilibrium populations, often with known inbreeding coefficients (F) or fixation indices (F_IS or F_ST). Here, we propose a novel null allele estimator that can be used to estimate the null allele frequency and adjust visible allele frequencies in populations for which independent estimates of F, F_IS or F_ST are available. The algorithm is currently available as an Excel macro that can be downloaded at no cost from http://www.microchecker.hull.ac.uk/ and will be incorporated into the software micro ‐checker .     

Polymorphism of the Dopamine Transporter Gene in Populations of the Volga–Ural Region

Polymorphism at the dopamine transporter gene (DAT1) in populations of the Volga–Ural region was examined by means of polymerase chain reaction. Statistically significant differences in the dopamine transporter gene allele and genotype frequency distribution were revealed both between the populations belonging to one ethnic group and between the populations from different linguistic families.     

Polymorphisms of cytochrome P450 1A1, glutathione s-transferases M1 and T1 genes in Ouangolodougou (Northern Ivory Coast)

In this study, the frequencies of CYP1A1, GSTM1, and GSTT1 gene polymorphisms were determined in 133 healthy individuals from Ouangolodougou, a small rural town situated in the north of the Ivory Coast. As appeared in several published studies, ethnic differences in these frequencies have been found to play an important role in the metabolism of a relevant number of human carcinogens. In the studied sample, the frequencies of Ile/Ile (wild type), Ile/Val (heterozygous variant), and Val/Val (homozygous variant) CYP1A1 genotypes were 0.271, 0.692, and 0.037, respectively. Frequencies of GSTM1 and GSTT1 null genotypes were 0.361 and 0.331, respectively. No significant differences were noted between men and women. In contrast to published data for Africans, CYP1A1 *Val Allele frequency (0.383) was significantly high (p < 0.001) in this specific population. For the GSTT1 null genotype, no differences were found between the studied and other African populations, the contrary to what occurred for the GSTM1 null genotype in relation to Gambia and Egypt.     

Analysis of genetic predisposition to pulmonary tuberculosis in native Russians

Tuberculosis (TB) is one of the most important concerns of public health. There is evidence suggesting that genetic status is responsible for predisposition to infectious diseases including TB. To determine genetic risk factors of TB development, the frequencies of polymorphisms of genes CYP1A1, CYP2D6, CYP2C9, CYP2C19, GSTT1, GSTM1, NAT2, MDR1, and NRAMP1 in 73 TB patients and 352 healthy individuals were determined by allele-specific hybridizatio n using microarray technology. The TB patients have shown a significant increase in the frequency of the null GSTT1 genotype (OR = 3.26, 95% CI = 1.91–5.55, p = 0.000028) as well as the double null GSTT1/GSTM1 genotype (OR = 4.05, 95% CI = 2.14-7.65,p = 0.000034) compared to the group of healthy donors. It was shown that the NAT2* 5/* 5 genotype in combination with the “null” GSTT1 and the double “null” GSTT1/GSTM1 genotypes was observed significantly more often in the TB patients than in the control sample. Thus the examined GSTT1, GSTM1 and NAT2 gene polymorphisms may potentially alter the risk of TB development in ethnic Russians and are of interest for further research using larger cohorts of patients.     

Influence of glutathione S-transferase polymorphisms (GSTT1, GSTM1, GSTP1) on type-2 diabetes mellitus (T2D) risk in an endogamous population from north India

Glutathione S-transferases (GSTs) belong to a group of multigene and multifunctional detoxification enzymes, which defend cells against a wide variety of toxic insults and oxidative stress. Oxidative stress leads to cellular dysfunction which contributes to the pathophysiology of diseases such as cancer, atherosclerosis, and diabetes mellitus. It is important to assess whether the glutathione S-Transferase (GSTT1, GSTM1 and GSTP1) genotypes are associated with type 2 diabetes mellitus as deletion polymorphisms have an impaired capability to counteract the oxidative stress which is a feature of diabetes. GSTT1, GSTM1 and GSTP1 gene polymorphisms were analysed in 321 patients and 309 healthy controls from an endogamous population from north India. An association analysis was carried out at two levels (a) individual genes and (b) their double and triple combinations. The proportion of GSTT1 and GSTM1 null genotypes was higher in diabetics compared to controls (GSTT1 30.8 vs. 21.0 %; GSTM1 49.5 vs. 27.2 %). The frequency of the null genotype at both loci was higher in diabetics (19.6 vs. 7.8 %) leading to an odds ratio of 2.90 (CI 1.76–4.78, P < 0.0001). At GSTP1locus, patients had a higher frequency of the V/V genotype (15.6 vs. 7.5 %) and significant susceptible odds ratio (2.56, CI 1.47–4.48, P < 0.001). A combination of null genotypes at GSTT1 and GSTM1 loci and V/V genotype of GSTP1 locus showed highest odds ratio (9.64, CI 1.53–60.63, P < 0.01). Overall this study highlights that GST genes may play an important role in the pathogenesis of type 2 diabetes. The risk is higher in individuals carrying more than one susceptible genotype at these loci. The potential role of GST polymorphisms as markers of susceptibility to type 2 diabetes needs further investigations in a larger number of patients and populations.     

The investigation of allele and genotype frequencies of <Emphasis Type="Italic">CYP3A5 (1*/3*)</Emphasis> and <Emphasis Type="Italic">P2Y12</Emphasis> (T744C) in Iran

Research on the frequency of the highly functional mutations of genes coding required for metabolizing enzymes has shown significant ethnic variations. However, few studies, if any, have examined the frequency distribution of major allelic variations in the context of Iran. In this regard, the present study focused on the genotype profile of Southern Iranians in order to compare allele frequencies of their CYP3A5 and P2Y12 (T744C) which have been shown to have roles in metabolizing clopidogrel, with those of other populations. Therefore, genotyping was carried out on 112 unrelated individuals by PCR–RFLP. The CYP3A5*3 allele was found in 185 persons with allelic frequency 0.82, which is the most common allele among Caucasians (90–95%). The frequency of 82% is different from other Caucasians (90–94%), Indians (67%), Vietnam (67%) and Africans (15%). but lower than frequency in Chinese populations (74%) and Korean (76%). The allele frequency of the −744T (4%) is different from frequencies of Caucasian, American, Chinese, Korean, and Subsahara population. This study confirmed significant inter-ethnic differences in CYP3A5 and P2Y12 frequencies between Iranians and other ethnic groups. The results of this study will be useful for clinical pharmacokinetic investigations and drug dosage recommendations especially antiplatelet drugs such as Clopidogrel, for Iranians.     

Glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genetic polymorphisms and atopic asthma in children from Southeastern Brazil

Xenobiotics can trigger degranulation of eosinophils and mast cells. In this process, the cells release several substances leading to bronchial hyperactivity, the main feature of atopic asthma (AA). GSTM1 and GSTT1 genes encode enzymes involved in the inactivation of these compounds. Both genes are polymorphic in humans and have a null variant genotype in which both the gene and corresponding enzyme are absent. An increased risk for disease in individuals with the null GST genotypes is therefore, but this issue is controversial. The aim of this study was to investigate the influence of the GSTM1 and GSTT1 genotypes on the occurrence of AA, as well as on its clinical manifestations. Genomic DNA from 86 patients and 258 controls was analyzed by polymerase chain reaction. The frequency of the GSTM1 null genotype in patients was higher than that found in controls (60.5% versus 40.3%, p = 0.002). In individuals with the GSTM1 null genotype the risk of manifested AA was 2.3-fold higher (95%CI: 1.4-3.7) than for others. In contrast, similar frequencies of GSTT1 null and combined GSTM1 plus GSTT1 null genotypes were seen in both groups. No differences in genotype frequencies were perceived in patients stratified by age, gender, ethnic origin, and severity of the disease. These results suggest that the inherited absence of the GSTM1 metabolic pathway may alter the risk of AA in southeastern Brazilian children, although this must be confirmed by further studies with a larger cohort of patients and age-matched controls from the distinct regions of the country.     

Genetic polymorphisms in GSTM1, GSTT1, GSTP1, GSTM3 and the susceptibility to gallbladder cancer in North India

Abstract

The glutathione S-transferase (GSTs) are polymorphic supergene family of detoxification enzymes that are involved in the metabolism of numerous potential carcinogens. Several allelic variants of polymorphic GSTs show impaired enzyme activity and are suspected to increase the susceptibility to various cancers. To find out the association of GST variants with risk of gallbladder cancer, the distribution of polymorphisms in the GST family of genes (GSTT1, GSTM1, GSTP1, and GSTM3) were studied in 106 cancer patients and 201 healthy controls. Genotypes were analysed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP). The frequencies of GSTM1 null and GSTM3*BB genotypes did not differ between patients and controls. The overall frequency of GSTT1 null was lower in cases as compared with controls (p=0.003, Odds ratio (OR)?=?0.2, 95% confidence interval (CI), 0.1–0.6). After sex stratification, the GSTT1 null frequency was reduced only in female patients (p=0.008, OR?=?0.2, 95% CI?=?0.1–0.6). However, the GSTP1, ile/val genotype and the val allele were significantly higher in cases than controls (p=0.013, OR?=?1.9, 95% CI?=?1.1–3.1; p=0.027, OR?=?1.5, 95% CI?=?1.0–2.1), respectively. To study gene–gene interactions, a combined risk of gallbladder cancer due to ile/val or val/val were calculated in combination with null alleles of GSTM1 and GSTT1 or the *B allele of GSTM3, but there was no enhancement of risk. Gallstones were present in 57.5% of patients with gallbladder cancer, but there were no significant differences between allelic/genotype frequencies of the studied GST genes polymorphisms between patients with or without gallstones. To best of our knowledge, this is the first paper showing ile/val genotypes and val allele of GSTP1 to be associated with higher risk of gallbladder cancer.     

Frequencies of GSTM1, GSTT1, and GSTP1 polymorphisms in a Brazilian population

The glutathione S-transferase (GST) family of enzymes has a vital role in phase II of biotransformation of environmental carcinogens, pollutants, drugs and other xenobiotics. GSTs are polymorphic, with the type and frequency of polymorphism being ethnic dependent. Polymorphisms in GST genes have been shown to be associated with susceptibility to disease and disease outcome. We determined the frequencies of GSTM1, GSTT1 and GSTP1 polymorphisms in 591 volunteers who had been residents of Rio de Janeiro for at least six months. Blood was collected and DNA extracted by proteinase K/SDS digestion. Information about social habits and health problems was also recorded. GSTM1 and GSTT1 polymorphisms were analyzed by a PCR-Multiplex procedure, whereas GSTP1 polymorphism was analyzed by PCR-RFLP. We found that 42.1% (48.9% of whites and 34.2% of non-whites) of the individuals had the GSTM1 null genotype, whereas 25.4% (25.1% of whites and 25.7% of non-whites) had the GSTT1 null genotype. The genotypic distribution of GSTP1 was 49.7% I/I, 38.1% I/V, and 12.2% V/V, whereas the allelic frequencies were 0.69 for the Ile allele, and 0.31 for the Val allele. The frequencies of GST polymorphisms in this Brazilian population were found to be different from those observed in other populations, particularly of other South American countries.     

Distribution of killer cell immunoglobulin-like receptors (KIR) and their HLA-C ligands in two Iranian populations

Killer cell immunoglobulin-like receptors (KIR) gene frequencies vary between populations and contribute to functional variation in immune responses to viruses, autoimmunity and reproductive success. This study describes the frequency distribution of 12 variable KIR genes and their HLA-C ligands in two Iranian populations who have lived for many generations in different environments: the Azerbaijanis at high altitude and the Jonobi people at sea level. The results are compared with those published for other human populations and a large group of English Caucasians. Differences were seen in KIR and HLA-C group frequencies, in linkage disequilibrium and inhibitory/activating KIR ratios between the groups. Similarities with geographically close populations in the frequencies of the KIR A and B haplotypes and KIR AA genotype reflected their common ancestry. The extreme variability of the KIR gene family and their HLA-C ligands is highlighted and their importance in defining differences between geographically and culturally isolated communities subject to different environmental pressures who come from the same ethnic grouping.     

Ethnic differences in the association of the glutathione S-transferase T1 (GSTT1) null genotype and risk of gastric carcinoma: a systematic review and meta-analysis

We performed a systematic review and meta-analysis of the association between the glutathione S-transferase T1 (GSTT1) deletion polymorphism and gastric cancer risk in populations from different ethnic backgrounds, based on a comprehensive literature search of the MEDLINE, EMBASE, and COCHRANE libraries. Thirty-six individual case–control studies comprising 7,689 gastric cancer cases and 12,445 controls were included in our meta-analysis. Overall, the GSTT1 null genotype appeared to increase gastric cancer risk (OR 1.17, 95 % CI 1.06–1.31, p = 0.003). While Caucasian populations showed an association between the GSTT1 deletion polymorphism and gastric cancer risk (OR 1.27, 95 % CI 1.05–1.52, p = 0.01), Asian populations did not show such an association (p = 0.11). When stratified by quality assessment scores, a significant association between the GSTT1 deletion polymorphism and gastric cancer risk was observed only in the Caucasian high quality subgroup (OR 1.27 95 % CI 1.01–1.60, p = 0.05). Null genotypes for both GSTT1 and GSTM1 deletion polymorphisms also increased gastric cancer risk (OR 1.37, 95 % CI 1.04–1.80, p = 0.03). Our study suggests that the GSTT1 null genotype is associated with a significant increase in gastric cancer risk in Caucasians, but not in Asians. Further well-designed studies are required to confirm the association between GSTT1 polymorphisms and gastric cancer risk in relation to various clinicopathological factors in different ethnic groups, especially Caucasians.     

Frequencies of <Emphasis Type="Italic">CYP1B1</Emphasis> and <Emphasis Type="Italic">CYP2F1</Emphasis> polymorphic variants in three ethnic groups of Bashkortostan and in patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a multifactorial respiratory disorder. Members of the cytochrome P450 family catalyze oxidative metabolism of exogenous chemicals and activate their substrates into reactive intermediates that may initiate lung injury. The frequencies of CYP1B1 and CYP2F1 polymorphic markers were determined in healthy people from Bashkortostan and tested for association with COPD. Using PCR-RFLP, the polymorphic markers Leu432Val (CYP1B1) and c.14-15insC (CYP2F1) were studied in healthy Russians (N = 191), Tatars (N = 198), and Bashkirs (N = 78) and in Russian (N = 169) and Tatar (N = 137) COPD patients. The CYP2F1 genotype frequency distribution proved to differ between the three ethnic groups (χ 2 = 21.29, d.f. = 4, P = 0.0001), Tatars having a higher frequency of the c.14-15insC/c.14-15insC genotype (6.38%). The highest frequency (39.74%) of the heterozygous genotype was observed in Bashkirs. The frequency of the insertion-free CYP2F1 variant in Tatars with extremely severe COPD and onset after 55 years of age was significantly higher (87.5%) than in patients of the same age group with moderate or severe COPD (87.50% vs. 75.53%, χ 2 = 3.964, d.f. = 1, P = 0.046; OR = 2.268). The allele and genotype frequency distributions of the CYP1B1 Leu432Val polymorphism were similar in the Russian, Tatar, and Bashkir ethnic groups. Leu432Val of CYP1B1 was not associated with COPD.     

A meta-analysis of the relationship between glutathione S-transferase T1 null/presence gene polymorphism and the risk of lung cancer including 31802 subjects

The relationship between glutathione S-transferase T1 (GSTT1) null/presence gene polymorphism and the risk of lung cancer from the published reports are still conflicting. This study was conducted to evaluate the relationship between GSTT1 null/presence gene polymorphism and the risk of lung cancer using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on July 1, 2012, and eligible investigations were included and synthesized using meta-analysis method. 51 reports were recruited into this meta-analysis for the association of null genotype of GSTT1 with lung cancer susceptibility, consisting of 15,140 patients with lung cancer and 16,662 controls. There was a marked association between GSTT1 null genotype and lung cancer risk in overall populations (OR = 1.15, 95 % CI 1.04–1.27, P = 0.007). Furthermore, GSTT1 null genotype was associated with the lung cancer risk in Asians (OR = 1.47, 95 % CI 1.23–1.76, P < 0.0001). However, GSTT1 null genotype was not associated with the risk of lung cancer in Caucasians, Brazilian population and Africans. In conclusion, GSTT1 null genotype is associated with the lung cancer in overall populations and in Asians.     

Polymorphism of Glutathione S-Transferase M1 and P1 in Patients with Cystic Fibrosis and Chronic Respiratory Diseases

Polymorphism of GSTM1 and GSTP1 genes was studied in patients with cystic fibrosis (CF) and chronic bronchopulmonary diseases (CBPD) living in Bashkortostan. A combination of certain GSTM1 and GSTP1 genotypes accompanied by severe mutations inCFTRgene proved to intensify a pathologic process in respiratory organs of patients with CF; a combination of the normal GSTM1 and heterozygous I/V GSTP1 genotypes is the most favorable (OR = 4.49; ² = 11.53, P < 0.002). In patients with CBPD, a combination of the GSTM1null genotype and the homozygous GSTP1 V/V genotype is the most common (5.5% versus 1.3% in control; ² = 3.01, P = 0.08). The frequency of this genotype is highest in groups of patients with recurrent bronchitis (8.1%; P = 0.07; OR = 6.75) and bronchiectatic disease (BED) (9.1%, P > 0.10, OR = 7.65). A combination of the null GSTM1 andI/V GSTP1 genotypes was found in 40.0% of patients with chronic nonobstructive bronchitis (² = 4.87; P = 0.03; OR = 4.03). Among patients with BED, a proportion of individuals with the normal GSTM1 and I/V GSTP1 genotypes was increased (36.4% versus 19.4% in control). In patients with chronic obstructive pulmonary disease (COPD), the frequencies of the GSTM1 and GSTP1 genotype combinations virtually did not differ from those in the control group suggesting that COPD severity is not related to changes in activities of glutathione S-transferases M1 and P1.