Screening of Tpo Gene C.1708c<T And C.1978c<G Mutations In Iraqi Patients with Hypothyroidism and Thyroid Cancer
Keywords:
Hypothyroidism, Thyroid cancer, TPO, c.1708C<T, c.1987C<G, Mutations, LAN primersAbstract
Thirty seven patients (hypothyroidism, n=20 and thyroid cancer, n=17) and twenty five healthy individuals (control) were used in this study. These patients, who attended the endocrinologist in Nuclear Medicine Hospital and Al Yarmouk Nuclear Medicine Department in Baghdad, were selected during a period from July to October 2009.
Modified specific locked nucleic acid (LNA) primers were used for the detection of TPO gene mutations which include c.1708 C> T and c.1978 C>G. Seven mutations were found in TPO gene. Mutations involved transition cytosine by thymine at position 1708 of the exon 10 (c.1708C<T) were found in four thyroid cancer patients, while, transversion of cytosine by guanine at the position 1978 of exon 11 (c.1978C<G) were found in one thyroid cancer and two hypothyroidism patients. It can be concluded that the c.1708C<T and / or c.1978C<G mutant TPO in hypothyroidism and thyroid cancer patients studied are very likely to be properly expressed but lacks enzymatic activity.
References
Ahmed, M.; Al Saihati, B.; Greer, W.; Al Nuaim, A.; Bakheet, S. and Abdul, Kareem, A. M. (1995). A Study of 875 cases of thyroid cancer observed over a fifteen-year peroid (1975-1989) at the King Faisal Specialist Hospital and Research Centre. Ann. Saudi Med., 15:579-584.
Akslen, L. A.; Haldorsen, T.; Thoresen, S. O. and Glattre, E. (1993). Incidence pattern of thyroid cancer in Norway: influence of birth cohort and time period. Int. J. Cancer, 53: 183–187.
AL-Ramahi I. J., AL-Faisal A. H. M., Abudl-Reda I., Aouda N.3, AL-Atar R. and Barusrux S. (2012). Screening of g.IVS5+1G to a mutation of TG gene and thyroid hormone level among Iraqi thyroid disorders. Journal of Medical Genetics and Genomics 4(1):1 – 5.
AL-Faisal A.H.M. , AL-Ramahi I.J. , Abudl-Hassan I.A. ,Hamdan A.T. and Barusrux S. (2012). Detection of heterozygous c.1708C>T and c.1978C>G thyroid peroxidase (TPO) mutations in Iraqi patients with toxic and non toxic goiter. Comparative Pathology Journal , 21(89) : 1-7.
American Cancer Society. (2009). Cancer Facts and Figures. Atlanta Ga.
Aoki, Y.; Belin, R.M.; Clickner, R.; Jeffries, R.; Phillips, L. and Mahaffey, K. R. (2007). Serum TSH and total T4 in the United States population and their association with participant characteristics. Thyroid Dec., 17(12):1211-1223.
Bikker, H.; Baas, F. and de Vijlder, J. J. M. (1997). Molecular analysis of mutated thyroid peroxidase detected in patients with total iodide organification defects. J. Clin. Endocrinol. Metab., 82: 649–653.
Deladoey,J. ; Pfarr, N. ; Vuissoz ,J.M. ; Parma , J. ; Vassart , G. ; Biesterfeld , S. ; Pohlenz , J. and Vliet , G.V. (2008). Pseudodominant inheritance of goitrous congenital hypothyroidism caused by TPO mutations:Molecular and in silico studies. J.Clinical Endocrinology and Metabolism , 93(2):627.
Dos, S. I. and Swerdlow, A. J. (1993). Thyroid cancer epidemiology in England and Wales time trends and geographical distribution. Br. J. Cancer, 67: 330–340.
El-Helal, T. A.; Bener, A. and Galadari, I. (1997). Pattern of cancer in the United Arab Emirates refered to Al-Ain Hospital. Ann. Saudi Med., 17: 506-509.
Gabriel, B.; Thomas, A.; Kent, F. and Talavera, M. S. (2009). Thyroid Disease. Staff Neurologist, Neurology Service, Philadelphia Veterans. Affairs. Medical Center. Med. Rep., 8(1):16-19.
Hamosh, A.; Scott, A. F.; Amberger, J. S.; Bocchini, C. A. and McKusick, V. A. (2005). Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic. Acids. Res., 514-517.
Hector M.; Sebastian, A.; Carina, M. and Rivolta, C. M. ( 2010). Genetics and pheFnomics of hypothyroidism and goiter due to thyroglobulin mutations. Genetics Thyroid Dis., 322: 44-55.
Kajantie , E.; Phillips, D. I.; Osmond, C.; Barker, D. J.; Forsen, T. and Eriksson, J. G. (2006). Spontaneous hypothyroidism in adult women is predicted by small body size at birth and during childhood. J. Clin. Endocrinol. Metab., 91(12): 4953-4956.
Kotani, T.; Umeki, K.; Yamamoto, I.; Maesaka, H.; Tachibana, K. and Ohtaki, S. A. (1999). Novel mutation in the human thyroid peroxidase gene resulting in a total iodide organification. defect. J. Endocrinol., 160: 267-73.
Kreisman, S. H.; Hennessey, J. V. (1999). Consistent reversible elevations of serum creatinine levels in severe hypothyroidism. Arch. Intern. Med., 159 (1) 11: 79-82.
Kuliawat, R.; Ramos-Castaneda, J.; Liu, Y. and Arvan, P. (2005). Intracellular trafficking of thyroid peroxidase to the cell surface. J Biol Chem 280:27713–27718.
Maniatis, T.; Fritsch, E. and Sambrook, J. (1982). Molecular Cloning, A laboratory Manual. Spring Cold Harbor Laboratory Press. Cold Spring Harbor, N.Y.
Miller, S.; Dykes, D. and Polesky, H. (1988). A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acid Res., 16:1215.
Nordyke, R. A,; Gilbert, F. I. and Harada, A.S. (1988). Graves”disease: influence of age on clinical findings. Arch. Intern. Med.,148:626–631.
Old, J. M. (1996). Hemoglobinopathies, community clues to mutation detection. In: methods in molecular medicine: molecular diagnoses of genetic diseases. Edited by Elles, R., Hamana press Inc.,Totowa, N. J. P. p., 169-183.
Pettersson, B.; Adami, H. O.; Wilander, E. and Coleman, M. P. (1991). Trends in thyroid cancer incidence in Sweden, 1958–1981, by histo-pathological type. Int. J. Cancer., 48: 28–33.
Ruf, J. and Carayon, P. (2006). Structural and functional aspects of thyroid peroxidase. Arch Biochem Biophys 445:269–277.
Sambrook, J.; Fitsch, E. and Maniatis, T. (1989). Molecular cloning a laboratory Manual. 2nd edition. Cold Spring Harbor Laboratory Press. Cold Spring Harbor.
Sawin, C. T.; Castelli, W. P.; Hershman, J. M. and McNamara, P.; Bacharach, P. (1985). The aging thyroid. Thyroid deficiency in the Framingham Study. Arch. Intern. Med., 145(8): 1386-1388.
Shaha, A. R. (2007). TNM classification of thyroid carcinoma. World. J. Surg., 31(5): 879-887.
Sklar, C.; Whitton, J. and Mertens, A. ( 2000). Abnormalities of the thyroid in survivors of Hodgkin disease: Data from the Childhood Cancer Survivor Study. J. Clin. Endocrinol. Metab., 85: 3227-3232.
Sondik, E. J. (1998). Cancer & minorities learning from the difference in prevalence, survival and mortality. Cancer, 83: 1757-1764.
Spitz, M. R.; Sider, J. G.; Katz, R. L.; Pollack, E. S. and Newell, G. R. (1988). Ethnic patterns ofthyroid cancer incidence in the United States, 1973–1981. Int. J. Cancer., 42: 549–553.
Yardena, T. R.; Sunee , M.; Carrie, R. S. and Alina, G. (2007). Clinical and genetic characteristics of congenital hypothyroidism due to mutations in the thyroid peroxide as (TPO) gene in Israelis. Clin. Endo., 66 (5):695–702.
Ye, S.; Dhillon, S.; Ke, X.; Andrew, R.; Collins, N. and Ian, M. (2001). An efficient procedure for genotyping single nucleotide polymorphisms. Nucleic Acid Research, 29:17.
Zheng, T.; Holford, T. R.; Chen, Y.; Ma, J.Z.; Flannery, J. andLiu, W. (1996). Time trend and age-period-cohort effect on incidence of thyroid cancer in Connecticut, 1935–1992. Int. J. Cancer, 67: 504–509.
Akslen, L. A.; Haldorsen, T.; Thoresen, S. O. and Glattre, E. (1993). Incidence pattern of thyroid cancer in Norway: influence of birth cohort and time period. Int. J. Cancer, 53: 183–187.
AL-Ramahi I. J., AL-Faisal A. H. M., Abudl-Reda I., Aouda N.3, AL-Atar R. and Barusrux S. (2012). Screening of g.IVS5+1G to a mutation of TG gene and thyroid hormone level among Iraqi thyroid disorders. Journal of Medical Genetics and Genomics 4(1):1 – 5.
AL-Faisal A.H.M. , AL-Ramahi I.J. , Abudl-Hassan I.A. ,Hamdan A.T. and Barusrux S. (2012). Detection of heterozygous c.1708C>T and c.1978C>G thyroid peroxidase (TPO) mutations in Iraqi patients with toxic and non toxic goiter. Comparative Pathology Journal , 21(89) : 1-7.
American Cancer Society. (2009). Cancer Facts and Figures. Atlanta Ga.
Aoki, Y.; Belin, R.M.; Clickner, R.; Jeffries, R.; Phillips, L. and Mahaffey, K. R. (2007). Serum TSH and total T4 in the United States population and their association with participant characteristics. Thyroid Dec., 17(12):1211-1223.
Bikker, H.; Baas, F. and de Vijlder, J. J. M. (1997). Molecular analysis of mutated thyroid peroxidase detected in patients with total iodide organification defects. J. Clin. Endocrinol. Metab., 82: 649–653.
Deladoey,J. ; Pfarr, N. ; Vuissoz ,J.M. ; Parma , J. ; Vassart , G. ; Biesterfeld , S. ; Pohlenz , J. and Vliet , G.V. (2008). Pseudodominant inheritance of goitrous congenital hypothyroidism caused by TPO mutations:Molecular and in silico studies. J.Clinical Endocrinology and Metabolism , 93(2):627.
Dos, S. I. and Swerdlow, A. J. (1993). Thyroid cancer epidemiology in England and Wales time trends and geographical distribution. Br. J. Cancer, 67: 330–340.
El-Helal, T. A.; Bener, A. and Galadari, I. (1997). Pattern of cancer in the United Arab Emirates refered to Al-Ain Hospital. Ann. Saudi Med., 17: 506-509.
Gabriel, B.; Thomas, A.; Kent, F. and Talavera, M. S. (2009). Thyroid Disease. Staff Neurologist, Neurology Service, Philadelphia Veterans. Affairs. Medical Center. Med. Rep., 8(1):16-19.
Hamosh, A.; Scott, A. F.; Amberger, J. S.; Bocchini, C. A. and McKusick, V. A. (2005). Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic. Acids. Res., 514-517.
Hector M.; Sebastian, A.; Carina, M. and Rivolta, C. M. ( 2010). Genetics and pheFnomics of hypothyroidism and goiter due to thyroglobulin mutations. Genetics Thyroid Dis., 322: 44-55.
Kajantie , E.; Phillips, D. I.; Osmond, C.; Barker, D. J.; Forsen, T. and Eriksson, J. G. (2006). Spontaneous hypothyroidism in adult women is predicted by small body size at birth and during childhood. J. Clin. Endocrinol. Metab., 91(12): 4953-4956.
Kotani, T.; Umeki, K.; Yamamoto, I.; Maesaka, H.; Tachibana, K. and Ohtaki, S. A. (1999). Novel mutation in the human thyroid peroxidase gene resulting in a total iodide organification. defect. J. Endocrinol., 160: 267-73.
Kreisman, S. H.; Hennessey, J. V. (1999). Consistent reversible elevations of serum creatinine levels in severe hypothyroidism. Arch. Intern. Med., 159 (1) 11: 79-82.
Kuliawat, R.; Ramos-Castaneda, J.; Liu, Y. and Arvan, P. (2005). Intracellular trafficking of thyroid peroxidase to the cell surface. J Biol Chem 280:27713–27718.
Maniatis, T.; Fritsch, E. and Sambrook, J. (1982). Molecular Cloning, A laboratory Manual. Spring Cold Harbor Laboratory Press. Cold Spring Harbor, N.Y.
Miller, S.; Dykes, D. and Polesky, H. (1988). A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acid Res., 16:1215.
Nordyke, R. A,; Gilbert, F. I. and Harada, A.S. (1988). Graves”disease: influence of age on clinical findings. Arch. Intern. Med.,148:626–631.
Old, J. M. (1996). Hemoglobinopathies, community clues to mutation detection. In: methods in molecular medicine: molecular diagnoses of genetic diseases. Edited by Elles, R., Hamana press Inc.,Totowa, N. J. P. p., 169-183.
Pettersson, B.; Adami, H. O.; Wilander, E. and Coleman, M. P. (1991). Trends in thyroid cancer incidence in Sweden, 1958–1981, by histo-pathological type. Int. J. Cancer., 48: 28–33.
Ruf, J. and Carayon, P. (2006). Structural and functional aspects of thyroid peroxidase. Arch Biochem Biophys 445:269–277.
Sambrook, J.; Fitsch, E. and Maniatis, T. (1989). Molecular cloning a laboratory Manual. 2nd edition. Cold Spring Harbor Laboratory Press. Cold Spring Harbor.
Sawin, C. T.; Castelli, W. P.; Hershman, J. M. and McNamara, P.; Bacharach, P. (1985). The aging thyroid. Thyroid deficiency in the Framingham Study. Arch. Intern. Med., 145(8): 1386-1388.
Shaha, A. R. (2007). TNM classification of thyroid carcinoma. World. J. Surg., 31(5): 879-887.
Sklar, C.; Whitton, J. and Mertens, A. ( 2000). Abnormalities of the thyroid in survivors of Hodgkin disease: Data from the Childhood Cancer Survivor Study. J. Clin. Endocrinol. Metab., 85: 3227-3232.
Sondik, E. J. (1998). Cancer & minorities learning from the difference in prevalence, survival and mortality. Cancer, 83: 1757-1764.
Spitz, M. R.; Sider, J. G.; Katz, R. L.; Pollack, E. S. and Newell, G. R. (1988). Ethnic patterns ofthyroid cancer incidence in the United States, 1973–1981. Int. J. Cancer., 42: 549–553.
Yardena, T. R.; Sunee , M.; Carrie, R. S. and Alina, G. (2007). Clinical and genetic characteristics of congenital hypothyroidism due to mutations in the thyroid peroxide as (TPO) gene in Israelis. Clin. Endo., 66 (5):695–702.
Ye, S.; Dhillon, S.; Ke, X.; Andrew, R.; Collins, N. and Ian, M. (2001). An efficient procedure for genotyping single nucleotide polymorphisms. Nucleic Acid Research, 29:17.
Zheng, T.; Holford, T. R.; Chen, Y.; Ma, J.Z.; Flannery, J. andLiu, W. (1996). Time trend and age-period-cohort effect on incidence of thyroid cancer in Connecticut, 1935–1992. Int. J. Cancer, 67: 504–509.
Published
2013-06-30
How to Cite
A.H.M., A.-F., I.A., A.-H., J., A.-R. I., & S., B. (2013). Screening of Tpo Gene C.1708c<T And C.1978c<G Mutations In Iraqi Patients with Hypothyroidism and Thyroid Cancer. Science Journal of University of Zakho, 1(1), 31–37. Retrieved from https://sjuoz.uoz.edu.krd/index.php/sjuoz/article/view/33
Issue
Section
Science Journal of University of Zakho
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License [CC BY-NC-SA 4.0] that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work, with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online.
