Hamid Nomani1,2, Lida Hagh-Nazari1,2, Ali Aidy1,3, Asad Vaisi-Raygani1,2, Amir Kiani1,2, Zohreh Rahimi4, Fariborz Bahrehmand1,2, Ebrahim Shakiba1,2, Hamid Reza Mozaffari5, Heidar Tavilani6, Tayebeh Pourmotabbed7. 1. a Fertility and Infertility Center Research, Kermanshah University of Medical Sciences , Kermanshah , Iran. 2. b Department of Clinical Biochemistry , Medical School, Kermanshah University of Medical Sciences , Kermanshah , Iran. 3. e Biotechnology and Medicinal Plant Research Center, Ilam University of Medical Sciences , Ilam , Iran. 4. c Medical Biology Research Center, Kermanshah University of Medical Sciences , Kermanshah , Iran. 5. f Department of Oral Medicine , School of Dentistry, Kermanshah University of Medical Sciences , Kermanshah , Iran. 6. g Urology and Nephrology Research Center, Hamadan University of Medical Sciences , Hamadan , Iran. 7. d Department of Microbiology, Immunology, and Biochemistry , University of Tennessee Health Science Center , Memphis , TN , USA.
Abstract
INTRODUCTION: There are some evidences indicating DNA damage by oxidant and mutant agents has an essential role in the chronic renal failure and end stage renal disease (ESRD). To investigate the possible association of GSTs variants with ESRD, we investigated the frequency of GST- T1, M1, and P1 genotypes, and the level of malondialdehyde (MDA) in patients with ESRD. MATERIALS AND METHODS: The present case-control study consisted of 136 ESRD patients treated with maintenance hemodialysis and 137 gender- and age-matched, unrelated healthy controls from the population of west of Iran. The GST- T1, M1, and P1 genotypes were determined in all individuals using multiplex-PCR and PCR-RFLP. The level of MDA was measured by high-performance liquid chromatography (HPLC). RESULTS: We found that GSTM1 and GSTT1 null genotypes (GSTT1-/GSTM1-) increased the risk of ESRD by 1.8 times (p < 0.001) and the increased risk of ESRD for GSTM-null (T1+-M1-) genotype was 3.04 times (p = 0.002). ESRD patients carriers the GST (GSTM1-null + GSTT1-null + GST-null) genotypes compared to GST normal genotype increased the risk of ESRD by 3.3 (p < 0.001) times. ESRD patients carriers of GST-null, GSTM1-null, and GSTT1-null genotypes had greater MDA concentration compared with the same genotypes of control subjects. Our results indicated that the GST-null allele (GSTT1-null/GSTM1-null) is a risk factor for ESRD and carriers of this allele have high levels of MDA. CONCLUSION: Our findings indicate that oxidative stress, impairment of the antioxidant system and abnormal lipid metabolism may play a role in the pathogenesis and progression of ESRD and its related complications. These data suggest that patients with ESRD are more susceptible to vascular diseases.
INTRODUCTION: There are some evidences indicating DNA damage by oxidant and mutant agents has an essential role in the chronic renal failure and end stage renal disease (ESRD). To investigate the possible association of GSTs variants with ESRD, we investigated the frequency of GST- T1, M1, and P1 genotypes, and the level of malondialdehyde (MDA) in patients with ESRD. MATERIALS AND METHODS: The present case-control study consisted of 136 ESRDpatients treated with maintenance hemodialysis and 137 gender- and age-matched, unrelated healthy controls from the population of west of Iran. The GST- T1, M1, and P1 genotypes were determined in all individuals using multiplex-PCR and PCR-RFLP. The level of MDA was measured by high-performance liquid chromatography (HPLC). RESULTS: We found that GSTM1 and GSTT1 null genotypes (GSTT1-/GSTM1-) increased the risk of ESRD by 1.8 times (p < 0.001) and the increased risk of ESRD for GSTM-null (T1+-M1-) genotype was 3.04 times (p = 0.002). ESRDpatients carriers the GST (GSTM1-null + GSTT1-null + GST-null) genotypes compared to GST normal genotype increased the risk of ESRD by 3.3 (p < 0.001) times. ESRDpatients carriers of GST-null, GSTM1-null, and GSTT1-null genotypes had greater MDA concentration compared with the same genotypes of control subjects. Our results indicated that the GST-null allele (GSTT1-null/GSTM1-null) is a risk factor for ESRD and carriers of this allele have high levels of MDA. CONCLUSION: Our findings indicate that oxidative stress, impairment of the antioxidant system and abnormal lipid metabolism may play a role in the pathogenesis and progression of ESRD and its related complications. These data suggest that patients with ESRD are more susceptible to vascular diseases.
Entities:
Keywords:
Glutathione s-transferase; end stage renal disease; hemodialysis; malondialdehyde; polymorphism
Authors: Paul Perco; Wenjun Ju; Julia Kerschbaum; Johannes Leierer; Rajasree Menon; Catherine Zhu; Matthias Kretzler; Gert Mayer; Michael Rudnicki Journal: JCI Insight Date: 2019-06-20
Authors: Shahid M Baba; Arshad A Pandith; Zafar A Shah; Sajad A Geelani; Javid R Bhat; Ayaz Gul; Sameer A Guru; Hamed A El-Serehy; Abid M Koul; Sheikh Mansoor Journal: Front Oncol Date: 2021-10-14 Impact factor: 6.244