Modulation of the GSTT1 activity by the GSTM1 phenotype in a sample of Italian farm-workers

Fuciarelli, Maria; Caccuri, Anna Maria; Francesca, Maria; Ferazzoli, Flavia; Piacentini, Sara; Porreca, Flavia

doi:10.1007/s00204-008-0334-6

Cited by 26 publications

(17 citation statements)

References 16 publications

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“…Furthermore, a significant interaction between the GSTM1 positive genotype and other GST variants has been highlighted in the genotoxic effect analysis of tobacco smoke (31). The inducibility of the GST system may explain the interactions between GST enzymes (32). The GSTA1*-69C/T variant causes a deficiency expression in the GSTA1 enzymes.…”

Section: Discussionmentioning

confidence: 98%

Glutathione S-transferase genes and the risk of recurrent miscarriage in Italian women

Polimanti

Piacentini

Lazzarin

et al. 2012

Fertility and Sterility

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Section: Discussionmentioning

confidence: 98%

Glutathione S-transferase genes and the risk of recurrent miscarriage in Italian women

Polimanti

Piacentini

Lazzarin

et al. 2012

Fertility and Sterility

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“…Compensatory up-regulation of other genes may occur in the absence of functional GSTM1 and GSTT1 enzymes. The GSTM1*0/*0 genotype has been associated with a significant increase in GSTT1 activity after xenobiotic exposure among Italian farm workers [14]. The authors conclude that the finding suggests a regulative mechanism common to the two enzymes.…”

Section: Discussionmentioning

confidence: 93%

“…One study found the GSTM1*0/*0 genotype to be associated with a significant increase in GSTT1 activity after exposure to xenobiotics. Subjects with the GSTM1*0/*0/GSTT1*1 genotype had higher enzyme activity than subjects with GSTM1*1/ GSTT1*1 indicating potential overcompensation [14]. Whether overcompensation also takes place during OC exposure in women lacking one of the GSTM1 or GSTT1 genes is currently unknown.…”

Section: Introductionmentioning

confidence: 97%

Interactions between oral contraceptive status and GSTM1 and GSTT1 deletions on insulin-like growth factor-1 (IGF-1) plasma levels in young healthy women

Henningson

Hietala

Bågeman

et al. 2010

Growth Hormone & IGF Research

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Access to the published version may require journal subscription. Published with permission from: ElsevierInteractions between oral contraceptive status and GSTM1 and GSTT1 deletions on insulin-like growth factor-1 (IGF-1) plasma levels in young healthy women Abstract Objective: Insulin-like growth factor-1 (IGF-1) is essential for the pubertal growth spurt and for normal mammary gland development. IGF-1 increases premenopausal breast cancer risk. Oral contraceptives (OCs) decrease IGF-1 in most women. The endogenous estrogens and their metabolites also influence IGF-1 levels. Glutathione S-transferases (GSTs) are involved in estrogen metabolism. We aimed to study IGF-1 levels and body size in relation to GSTM1 and GSTT1 deletions, and GSTP1*1B and current oral contraceptive (OC) status. Design: Questionnaires on reproductive factors and OC use were completed and blood samples were obtained during menstrual cycle day 18-23 in healthy women (≤40 years) from breast cancer high-risk families. IGF-1 was analyzed with radioimmunoassay. Genetic analyses were done with PCR based methods. Initially 258 women were included. After exclusion 229 women were finally included in the analyses of IGF-1 in relation to GSTM1 and GSTT1. Results: Among the 142 non-OC users, GSTM1*0/*0 or GSTT1*0/*0 alone were associated with lower IGF-1 levels while homozygous GSTM1*0/*0/GSTT1*0/*0 carriers had higher IGF-1 levels (P interaction =0.024). In the 87 OC users, GSTM1*0/*0 or GSTT1*0/*0 alone were associated with higher IGF-1 levels while homozygous GSTM1*0/*0/GSTT1*0/*0 carriers had lower IGF-1 levels (P interaction =0.010). Among all 229 women, a three-way interaction model showed an interaction between the GSTM1*0/*0/GSTT1*0/*0 genotype and OC use on IGF-1 levels (P interaction =0.003). GSTP1*1B was not associated with IGF-1. The GSTM1*1/GSTT1*0/*0 genotype was associated with high body weight (P=0.003) and GSTM1*0/*0/GSTT1*0/*0 was associated with early growth (P=0.003). Conclusion: Both OC use and GSTT1 and GSTM1 genotypes may influence IGF-1 levels. Further studies are warranted to confirm our finding and elucidate the clinical importance.

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“…However the loss of GSTT1 enzyme activity by deletion polymorphism can affect other metabolic pathways that could be strongly activated, for example other genes in the GST family, thus causing the pre-ventive effect on osteoblast cells. This fact could be supported, however indirectly, by the study of Fuciarelli et al [32] who hypothesized that there is probably a regulative compensatory mechanism that involves the increased activity of GSTT1 enzyme when the GSTM1 enzyme is lacking. Further studies are needed on the activities of GSTT1 and GSTM1 and their relation to deletion genotypes.…”

Section: Discussionmentioning

confidence: 99%

Opposite Effects ofGSTM1– andGSTT1– Gene Deletion Variants on Bone Mineral Density

et al. 2011

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Abstract.Oxidative stress is associated with osteoporosis. The glutathione S-transferases form the major detoxifying group of enzymes responsible for eliminating products of oxidative stress. We have therefore proposed GSTM1 and GSTT1 genes as candidates for studying the genetics of osteoporosis. The aim of the present study was to examine possible association of GSTM1 and GSTT1 gene deletion polymorphisms, alone or in combination, with bone mineral density at femoral neck (BMD fn), lumbar spine (BMD ls) and total hip (BMD th) in Slovenian elderly women and men. GSTM1 and GSTT1 gene deletion polymorphisms in 712 elderly people were analyzed using the triplex PCR method for the presence of GSTM1 and GSTT1 gene segments. BMD fn, BMD ls and BMD th were measured by the dual-energy X-ray absorptiometry (DEXA) method. Results were analyzed using univariate statistic model adjusted for sex, body mass index (BMI) and age. Our results showed the significant differences in BMD th, BMD ls and BMD fn values (p = 0.031, 0.017 and 0.023, respectively) in subgroups of GSTT1 gene deletion polymorphism. For GSTM1 gene deletion polymorphism borderline significant association was found with BMD ls (p = 0.100). Furthermore, subjects with homozygous deletion of GSTT1 gene showed higher BMD values on all measured skeletal sites and, in contrast, subjects with homozygous deletion of GSTM1 gene showed lower BMD values. Moreover, a gene-gene interaction study showed significant association of GSTM1-null and GSTT1-null polymorphisms with BMD ls values (p = 0.044). Carriers with a combination of the presence of GSTT1 gene and the homozygous absence of GSTM1 gene fragment were associated with the lower BMD values at all skeletal sites. The significant association of combination of GSTT1 gene presence and homozygous absence of GSTM1 gene with BMD was demonstrated, suggesting that it could be used, if validated in other studies, as genetic marker for low BMD.

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Modulation of the GSTT1 activity by the GSTM1 phenotype in a sample of Italian farm-workers

Cited by 26 publications

References 16 publications

Glutathione S-transferase genes and the risk of recurrent miscarriage in Italian women

Glutathione S-transferase genes and the risk of recurrent miscarriage in Italian women

Interactions between oral contraceptive status and GSTM1 and GSTT1 deletions on insulin-like growth factor-1 (IGF-1) plasma levels in young healthy women

Opposite Effects ofGSTM1– andGSTT1– Gene Deletion Variants on Bone Mineral Density

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