ABB  Vol.4 No.6 , June 2013
Proline-leucine polymorphism of human glutathione peroxidase 1 in Thalassemia major
ABSTRACT

Thalassemia is associated with low antioxidant enzyme deficiency especially glutathione peroxidase. GPX exists in 6 isomeric forms out of which GPX1 Single Nucleotide Polymorphism is found to be associated with Thalassemia major. In our study, the determination of the allelic frequency and phenotype of a common polymorphism in Se-dependent glutathione peroxidase 1 (GPX1) was observed in Thalassemic populations. A proline/leucine variant occurs at position 197 close to the C-terminus of the protein. The genotypes encoding Pro/Pro, Pro/Leu, and Leu/ Leu are distributed according to the Hardy-Weinberg relationship. The study has been carried out in 40 Thalassemic cases and 40 control subjects. No significant association between allele frequency and risk to get fatal was evident. Erythrocyte GPX activity was determined and no significant differences were obtained between the genotypes. It can be concluded that the Pro/Leu genetic variation does not appear to compromise the defense against oxidative stress in red blood cells or to be associated with significant pathology.


Cite this paper
Bhargava, V. , Gulati, M. , Singh, N. and Bhargava, R. (2013) Proline-leucine polymorphism of human glutathione peroxidase 1 in Thalassemia major. Advances in Bioscience and Biotechnology, 4, 699-701. doi: 10.4236/abb.2013.46091.
References
[1]   [1] Holben, D.H. and Smith, A.M. (1999) The diverse role of selenium within selenoproteins: A review.Journal of the American Dietetic Association, 99, 836-843. doi:10.1016/S0002-8223(99)00198-4

[2]   Fu, Y., Cheng, W.H., Porres, J.M., Ross, D.A. and Lei, X.G. (1999) Knockout of cellular glutathione peroxidase gene renders mice susceptible to diquatinduced oxidative stress.Free Radical Biology and Medicine, 27, 605-611.

[3]   Halliwell, B. (1999) Antioxidant defence mechanisms: From the beginning to the end (of the beginning). Free Radical Research, 31, 261-272. doi:10.1080/10715769900300841

[4]   Halliwell, B. and Cross, C.E. (1994) Oxygen-derived species: Their relation to human disease and environmental stress. Environmental Health Perspectives, 102, 5-12. doi:10.2307/3432205

[5]   Sohal, R.S. and Weindruch, R. (1996) Oxidative stress, caloric restriction, and aging. Science, 273, 59-63. doi:10.1126/science.273.5271.59

[6]   Riemersma, R.A., Oliver, M., Elton, R.A., Alfthan, G., Vartiainen, E., Salo, M., Rubba, P., Mancini, M., Georgi, H. and Vuilleumier, J.P. (1990) Plasma antioxidants and coronary heart disease: Vitamins C and E, and selenium. European journal of clinical nutrition, 44, 143-150.

[7]   Eichholzer, M., Stahelin, H.B. and Gey, K.F. (1992) Inverse correlation between essential antioxidants in plasma and subsequent risk to develop cancer, ischemic heart disease and stroke respectively: 12-year follow-up of the Prospective Basel Study. EXS, 62, 398-410.

[8]   Foy, C.J., Passmore, A.P., Vahidassr, M.D., Young, I.S. and Lawson, J.T. (1999) Plasma chain breaking antioxidants in Alzheimer’s disease, vascular dementia and Parkinson’s disease. International Journal of Medicine, 92, 39-45. doi:10.1093/qjmed/92.1.39

[9]   Yamamoto, Y., Yamashita, S., Fujisawa, A., Kokura, S. and Yoshikawa, T. (1998) Oxidative stress in patients with hepatitis, cirrhosis, and hepatoma evaluated by plasma antioxidants. Biochemical and Biophysical Research Communications, 247, 166-170. doi:10.1006/bbrc.1998.8752

[10]   Bolzan, A.D., Bianchi, M.S. and Bianchi, N.O. (1997) Superoxide dismutase, catalase and glutathione peroxidase activities in human blood: Influence of sex, age and cigarette smoking. Clinical Biochemistry, 30, 449-454. doi:10.1016/S0009-9120(97)00047-7

[11]   Omaye, S.T., Burri, B.J., Swendseid, M.E., Henning, S.M., Briggs, L.A., Bowen, H.T. and Ota, R.B. (1996) Blood antioxidants changes in young women following beta-carotene depletion and repletion. Journal of the American College of Nutrition, 15, 469-474.

[12]   Krajcovicova-Kudlackova, M., Simoncic, R., Babinska, K. and Bederova, A. (1995) Levels of lipid peroxidation and antioxidants in vegetarians. European Journal of Epidemiology, 11, 207-211. doi:10.1007/BF01719489

[13]   Brookes, A.J. (1999) The essence of SNPs. Gene, 234, 177-186. doi:10.1016/S0378-1119(99)00219-X

[14]   Forsberg, L., de Faire, U. and Morgenstern, R. (1999) Low yield of polymorphisms from EST blast searching: Analysis of genes related to oxidative stress and verification of the P197L polymorphism in GPX1. Human Mutation, 13, 294-300.

[15]   Hardell, L., Danell, M., Angqvist, C.A., Marklund, S.L., Fredriksson, M., Zakari, A.L. and Kjellgren, A. (1993) Levels of selenium in plasma and glutathione peroxidase in erythrocytes and the risk of breast cancer. A case— Control study. Biological Trace Element Research, 36, 99-108. doi:10.1007/BF02783168

[16]   Andersen, P.M., Nilsson, P., Forsgren, L. and Marklund, S.L. (1998) CuZn-superoxide dismutase, extracellular superoxide dismutase, and glutathione Peroxidase in blood from individuals homozygous for Asp90Ala CuZu-superoxide dismutase mutation. Journal of Neurochemistry, 70, 715-720. doi:10.1046/j.1471-4159.1998.70020715.x

[17]   WHO MONICA Project Principal Investigators (1998) The World Health Organization MONICA Project (Monitoring Trends and Determinants in Cardiovascular Disease): A major international collaboration. The Journal of Clinical Epidemiology, 41, 105-114.

[18]   Stegmayr, B. and Asplund, K. (1992) Measuring stroke in the population: Quality of routine statistics in comparison with a population-based stroke registry. Neuroepidemiology, 11, 204-213. doi:10.1159/000110933

[19]   Ahmed, E., Trifunovic, J., Stegmayr, B., Hallmans, G., and Lefvert, A.K. (1999) Autoantibodies against oxidatively modified LDL do not constitute a risk factor for stroke: A nested case—Control study. Stroke, 30, 25412546. doi:10.1161/01.STR.30.12.2541

[20]   Soderberg, S., Ahren, B., Stegmayr, B., Johnson, O., Wiklund, P.G., Weinehall, L., Hallmans, G. and Olsson, T. (1999) Leptin is a risk marker for first-ever hemorrhagic stroke in a population-based cohort. Stroke, 30, 328-337. doi:10.1161/01.STR.30.2.328

[21]   Forsberg, L., de Faire, U. and Morgenstern, R. (1998) To Identify Genetic Polymorphisms in the “Expressed Sequence Tag” (EST) Database. http://www.elsevier.com/locate/tto

[22]   Emahazion, T., Jobs, M., Howell, W.M., Siegfried, M., Wyoni, P.I., Prince, J.A. and Brookes, A.J. (1999) Identification of 167 polymorphisms in 88 genes from candidate neurodegeneration pathways. Gene, 238, 315-324. doi:10.1016/S0378-1119(99)00330-3

[23]   Moscow, J.A., Schmidt, L., Ingram, D.T., Gnarra, J., Johnson, B. and Cowan, K.H. (1994) Loss of heterozygosity of the human cytosolic glutathione Peroxidase I gene in lung cancer. Carcinogenesis, 15, 2769-2773. doi:10.1093/carcin/15.12.2769

[24]   Saugstad, O.D. and Marklund, S.L. (1988) High activities of erythrocyte glutathione peroxidase in patientswith the Lesch-Nyhan syndrome. Acta Medica Scandinavica, 224, 281-285.

 
 
Top