Role of GSTT1 and GSTM1 gene polymorphism for development of preeclampsia in Bangladeshi women

Abstract

Worldwide, pre‐eclampsia (PE) ranks as a major obstetric problem leading to substantial maternal and perinatal morbidity and mortality, especially in developing countries. Clinically it appears as a maternal syndrome, including hypertension and proteinuria after second half of pregnancy. PE affected by genetic trait, is associated with oxidative stress due to imbalance between the production of reactive oxygen species and the ability of antioxidant process. The glutathione S‐transferases (GST) are a group of enzymes which are involved in protecting cells from oxidative stress. In our study, we evaluated the risk of developing preeclampsia related to GSTT1 and GSTM1 genotypes. 104 patients having preeclampsia and 200 healthy controls having no history of preeclampsia were recruited for the study after getting written consent from them. DNA was extracted from the blood and Polymerase Chain Reaction (PCR) method was used to identify genotypes of GSTT1 and GSTM1 in study subjects. We used odds ratio to calculate the risk between cases and controls using SPSS 17. Genotype frequency of GSTM1 nul genotype showed significant difference between case and control group (p<0.001). Combined null genotype for GSTT1 and GSTM1 showed significant difference between two groups when compared to combined present genotype for GSTT1 and GSTM1 (p<0.001). There was significant association for GSTM1 null genotype with the development of preeclampsia (p<0.001) and the odds ratio was significantly higher in patients compared to control subjects (OR=4.75; 95% CI=2.17–10.39). For GSTT null genotype, there was increased risk for developing preeclampsia but the association was not significant (OR=1.22; 95% CI=0.58–2.57).In case of GSTT1 and GSTM1 combined genotype, patients having both null genotypes for GSTT1 and GSTM1 showed significance (p<0.001) and higher risk of developing preeclampsia when compared to control subjects (OR=7.64; 95% CI=2.38–24.60). We found a significant association between GSTM1 null genotype and the risk of developing preeclampsia in Bangladeshi population. No risk was found for GSTT1 null genotype and preeclampsia. For combined null genotype of GSTT1 and GSTM1, the risk was even higher relative to the risk of either GSTT1 null or GSTM1 null genotype alone.Support or Funding InformationDear colleague, I hereby, would like to express my motivation with this letter to attend the American Society for Biochemistry and Molecular Biology at San Diego, USA from 21–25 April 2018.The conference topics are relevant to my professional skills, and therefore I would welcome the opportunity to attend this conference having researchers from different countries of the world. I am working as an program coordinator at RHSTEP and at the same working as a predatory PhD student at Department of Biochemistry and Molecular Biology of Dhaka University.As a unique added value of this event, I will find a chance for networking with other scientists from different countries, which is an excellent opportunity for horizontal exchange of knowledge and experience. This networking will expand my opportunities for planning collaborative research projects in future.I have completed my MBBS from Moulana Bhasani Medical College and MPH from American International University, Bangladesh. In case of all three degrees, the medium of instruction was English.Unfortunately I do not have fund to attend this conference and I will apply for a travel grant.My attendance at this training will be very helpful for my carrier development and I would highly appreciate to be one of the selected participants.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The good Samaritan glutathione-S-transferase P1: An evolving relationship in nitric oxide metabolism mediated by the direct interactions between multiple effector molecules

“…Although the risk of developing preeclampsia was higher for patients with the GSTT1 genotype, it was not significant [68]. However, the risk of developing preeclampsia with a combined GSTM1 and GSTT1 genotype was much higher relative to the GSTM1 null genotype alone [68]. These results are similar to another study in Mexican mestizo populations that demonstrated that patients with the combined GSTM1/GSTT1 deletion genotype conferred a marginally higher risk of preeclampsia versus the controls [67].…”

“…Consistent with the interaction of DNICs with GSTs, it is interesting to discuss studies demonstrating the association between the GSTM1 and GSTT1 null genotype and NO-related disorders, including preeclampsia, hypertension, and atherogenesis [65][66][67][68]. A 2018 study of 104 patients with preeclampsia and 200 healthy controls identified a highly significant (p < 0.001) association between the GSTM1 null genotype and the development of preeclampsia [68].…”

“…A 2018 study of 104 patients with preeclampsia and 200 healthy controls identified a highly significant (p < 0.001) association between the GSTM1 null genotype and the development of preeclampsia [68]. Although the risk of developing preeclampsia was higher for patients with the GSTT1 genotype, it was not significant [68]. However, the risk of developing preeclampsia with a combined GSTM1 and GSTT1 genotype was much higher relative to the GSTM1 null genotype alone [68].…”

Glutathione-S-Transferases as Potential Targets for Modulation of Nitric Oxide-Mediated Vasodilation

“…Further studies examining the GSTs and their roles in regulating vasodilation via its interactions with NO could lead to new therapeutic avenues to treat hypertension and other related disorders. In particular, the GSTM1 null genotype has been associated with an increased risk of blood pressure-related disorders such as preeclampsia and hypertension [ 71 , 72 , 73 , 74 , 75 ]. Investigations exploring the interaction of GSTM1 with NO, especially as DNICs, and the impact on sGC activation would provide novel insights for the treatment of these conditions and potentially advance the development of new vasodilators.…”