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HNF1A Geni rs1169288 (A>C) Mutasyonunun MODY3 Üzerine Etkisinin Araştırılması

Year 2018, Issue: 1, 21 - 32, 30.09.2018

Abstract




Otozomal dominant kalıtımlı ve monogenik
bir diyabet formu olan Gençlerin Erişkin Başlangıçlı Diyabetinin (MODY) kliniği
ve gelişiminden sorumlu tanımlanmış mutasyonlar ve etkileri oldukça heterojendir.
Bu amaçla, çalışmamızda HNF1A gen
mutasyonları ile gelişen MODY3'te etken rs1169288 (c.79A>C, p.I27L)
yanlış anlamlı mutasyonunun hastalığın klinik ve biyokimyasal parametreleri
üzerine etkisinin incelenmesi hedeflenmiştir. Çalışmamızda 79 sağlıklı kontrol
ve 75 MODY ön tanılı hastada HNF1A rs1169288 mutasyonu yeni nesil
dizileme (NGS) ile incelenmiş ve mutasyonun klinik ve laboratuvar
parametrelerle ilişkisi SPSS(20.0) istatistik programıyla araştırılmıştır. HNF1A rs1169288
(A>C) mutasyonu genotiplerinin kontrol grubundaki etkileri
incelendiğinde mutant-CC genotipi taşıyan bireylerde A alleli taşıyanlara
kıyasla Gama glutamil transferaz (GGT) ve Hemoglobin (Hb) düzeylerinin (p=0,014;
p=0,027) yüksek; hasta grubunda ise, CC genotipi taşıyanlarda normal A alleli
taşıyanlara kıyasla başvuru kan şekerinin (BKŞ) yüksek (p=0,016) ve üre
düzeyinin düşük (p=0,022) olduğu gözlenmiştir (307,86±28,11 vs 175,65±25,59). Ancak
bu genotipin diğer klinik ve biyokimyasal parametreler üzerine anlamlı bir etkisi
gözlenmemiştir (p>0.05). Literatür çalışmaları yaygın MODY formlarından biri
olan MODY3 için hastalığın klinik tanısını kolaylaştıracak yeterli ayırt edici
parametre olmadığı yönündedir. Bu anlamda çalışmamız hastalığın klinik ve
biyokimyasal bulgularının anlamlandırılmasına katkı sağlamakta ve MODY
kliniğinde HNF1A rs1169288 mutasyonunun serum GGT, Hb, BKŞ ve üre düzeylerinde
etkili olabileceğine dikkat çekmektedir.




References

  • McDonald, T.J. ve Ellard, S. Maturity onset diabetes of the young: identification and diagnosis. Annals of Clinical Biochemistry, 50(5), (2013), 403–415.
  • Nakhla, M. ve Polychronakos, C. Monogenic and Other Unusual Causes of Diabetes Mellitus. Pediatric Clinics of North America, 52, (2005), 1637– 1650.
  • Velho, G. ve Froguel, P. Genetic, metabolic and clinical characteristics of maturity onset diabetes of the young. European Journal of Endocrinology, 138, (1998), 233±239.
  • Yılmaz-Ağladıoğlu, S., Aycan, Z., Çetinkaya, S., Baş, V.N., Önder, A., Peltek-Kendirci, H.N. ve ark. Maturity onset diabetes of youth (MODY) in Turkish children: sequence analysis of 11 causative genes by next generation sequencing. J Pediatr Endocrinol Metab. 29(4), (2016), 487–496.
  • Atabek, M.E. ve Kurtoglu, S. Gençlerin Erişkin Başlangıçlı Diabeti. Turkish Journal Of Medical Sciences, 24, (2004), 167-172.
  • Javadi, M., Rafatpanah, H., Taghavi, S. M., Tavakolafshari, J., Ganjali, R., Valizadeh, N. ve ark. Analysis of the glucokinase gene in Iranian families with maturity onset diabetes of the young. Journal of Diabetes Mellitus, 03(04), (2013), 192-198. doi:10.4236/jdm.2013.34029
  • Covantev, S., Chiriac, A., Perciuleac, L. ve Zozina, V. Maturity onset diabetes of the young: Diagnosis and treatment options, 5(4), (2016), e0402 doi: 10.15275/rusomj.2016.0402
  • Kahn, C.R., Weir, G.C., King, G.L., Moses, A.C., Smith, R.J. ve Jacobson, A.M. Joslin’s Diabetes mellitus. 14. Baskı. (2005). Chapter 22: Genetics of Type 2 Diabetes Lippincott Williams and Wilkins, sf 371-392.
  • Kim, S.H. Maturity-onset diabetes of the young: what do cli¬nicians need to know? Diabetes Metab J. 39, (2015), 468-77.
  • Prudente, S., Jungtrakoon, P., Marucci, A., Ludovico, O., Buranasupkajorn, P., Mazza, T, ve ark. Loss-of-Function Mutations in APPL1 in Familial Diabetes Mellitus. Am J Hum Genet, 97(1), (2015), 177-185. doi:10.1016/j.ajhg.2015.05.011
  • Ovsyannikova, A.K., Rymar, O.D., Shakhtshneider, E.V., Klimontov, V.V., Koroleva, E.A., Myakina, N.E. ve Voevoda, M.I. ABCC8-Related Maturity-Onset Diabetes of the Young (MODY12): Clinical Features and Treatment Perspective. Diabetes Ther, 7(3), (2016), 591-600. doi:10.1007/s13300-016-0192-9
  • Colclough, K., Bellanne-Chantelot, C., Saint-Martin, C., Flanagan, S.E., ve Ellard, S. Mutations in the Genes Encoding the Transcription Factors Hepatocyte Nuclear Factor 1 Alpha and 4 Alpha in Maturity-Onset Diabetes of the Young and Hyperinsulinemic Hypoglycemia. Hum Mutat, 34, (2013), 669–685.
  • Negahdar, M., Aukrust,I., Molnes, J., Solheim, M.H., Johansson, B.B., Sagen, J.V. ve ark. GCK-MODY diabetes as a protein misfolding disease: The mutation R275C promotes protein misfolding, self-association and cellular degradation. Biochim Biophys Acta. Nov; 1822(11), (2012), 1705-15. doi: 10.1016/j.bbadis.2012.07.005.
  • Hattersley, A.T ve Patel, K.A. Precision diabetes: learning from monogenic diabetes. Diabetologia, 60, (2017), 769-777. DOI 10.1007/s00125-017-4226-2
  • Gardner, D.S. ve Tai, E.S. Clinical features and treatment of maturity onset diabetes of the young (MODY). Diabetes Metab Syndr Obes, 5, (2012), 101-108. doi:10.2147/DMSO.S23353
  • Juszczak, A. ve Owen, K. Identifying subtypes of monogenicdiabetes. Diabetes Manage, 4(1), (2014), 49–61.
  • Kleinberger, J.W. ve Pollin, T.I. Undiagnosed MODY: Time for Action. Curr Diab Rep, 15(12), (2015), 110. doi:10.1007/s11892-015-0681-7
  • Beijers, H. J., Losekoot, M., Odink, R. J. ve Bravenboer, B. Hepatocyte nuclear factor (HNF)1A and HNF4A substitution occurring simultaneously in a family with maturity-onset diabetes of the young. Diabet Med, 26(11), (2009), 1172-1174. doi:10.1111/j.1464-5491.2009.02855.x
  • Forlani, G., Zucchini, S., Di Rocco, A., Di Luzio, R., Scipione, M., Marasco, E. ve ark. Double heterozygous mutations involving both HNF1A/MODY3 and HNF4A/MODY1 genes: a case report. Diabetes Care, 33(11), (2010), 2336-2338. doi:10.2337/dc10-0561
  • Lopez-Garrido, M.P., Herranz-Antolin, S., Alija-Merillas, M.J., Giralt, P. ve Escribano, J. Co-inheritance of HNF1a and GCK mutations in a family with maturity-onset diabetes of the young (MODY): implications for genetic testing. Clin Endocrinol (Oxf), 79(3), (2013), 342-347. doi:10.1111/cen.12050
  • Estalella, I., Rica, I., Perez de Nanclares, G., Bilbao, J.R., Vazquez, J.A., San Pedro, J.I. ve ark. Mutations in GCK and HNF-1alpha explain the majority of cases with clinical diagnosis of MODY in Spain. Clin Endocrinol (Oxf), 67(4), (2007), 538-546. doi:10.1111/j.1365-2265.2007.02921.x
  • Ellard, S. Hepatocyte nuclear factor 1 alpha (HNF-1-alpha) mutations in maturity-onset diabetes of the young. Hum. Mutat, 16, (2000), 377-385.
  • Gragnoli, C., Lindner, T., Cockburn, B.N., Kaisaki, P.J., Gragnoli, F. veMarozzi, G. ve ark. Maturity-Onset Diabetes of the Young Due to a Mutation in the Hepatocyte Nuclear Factor-4aBinding Site in the Promoter of the HepatocyteNuclear Factor-la Gene. Diabetes, 46, (1997), 1648-1651.
  • Bonnycastle, L.L., Willer, C.J., Conneely, K.N., Jackson, A.U. Burril, C.P., Watanabe, R.M., ve ark. Common Variants in Maturity-Onset Diabetes of the Young Genes Contribute to Risk of Type 2 Diabetes in Finns. Diabetes, 55, (2006), 2534–2540.
  • Holmkvist, J., Almgren, P., Lyssenko, V., Lindgren, C.M., Eriksson, K.F., Isomaa, B. ve ark. Common Variants in Maturity-Onset Diabetes of the Young Genes and Future Risk of Type 2 Diabetes. Diabetes, 7, (2008), 1738–1744.
  • Pruhova, S., Ek, J., Lebl, J., Sumnik, Z., Saudek, F., Andel, M., ve ark. Genetic epidemiology of MODY in the Czech republic: new mutations in the MODY genes HNF-4alpha, GCK and HNF-1alpha. Diabetologia, 46(2), (2003), 291-295. doi:10.1007/s00125-002-1010-7
  • Ryffel, G.U. Mutations in the human genes encoding the transcription factors of the hepatocyte nuclear factor (HNF)1 and HNF4 families: functional and pathological consequences. Journal of Molecular Endocrinology, 27, (2001), 11–29.
  • Morita, K.,Saruwatari, T., Tanaka, T., Oniki, K., Kajiwara, A., Otakeb, K.K., Ogatab, Y. ve ark. Associations between the common HNF1A gene variant p.I27L (rs1169288) and risk of type 2 diabetes mellitus are influenced by weight. Diabetes & Metabolism, (2014), 4 pages.
  • Giuffrida, F.M.A., Furuzawa, G.K., Kasamatsu, T.S., Oliveira, M.M., Reis, A.F. ve Dib S.A. HNF1A gene polymorphisms and cardiovascular risk factors in individuals with late-onset autosomal dominant diabetes: a cross-sectional study. Cardiovascular Diabetology, 8(28), (2009), 9 pages. doi:10.1186/1475-2840-8-28
  • Eide, S.A., Raeder, H., Johansson, S., Midthjell, K., Sovik, O., Njolstad, P.R.ve ark. Prevalence of HNF1A (MODY3) mutations in a Norwegian population (the HUNT2 Study). Diabet. Med. 25, (2008), 775–781. DOI: 10.1111/j.1464-5491.2008.02459.x
  • Reiner, A.P., Barber, M.J., Guan, Y., Ridker, P.M., Lange, L.A., Chasman, D.I., ve ark. Polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are associated with C-reactive protein. Am J Hum Genet., 82(5), (2012), 1193-201. doi: 10.1016/j.ajhg.2008.03.017.
  • Najmi, L.A., Aukrust, I., Flannick, J., Molnes, J., Burtt, N., Molven, A. ve ark. Functional Investigations of HNF1A Identify Rare Variants as Risk Factors for Type 2 Diabetes in the General Population. Diabetes, 66, (2017), 335–346. DOI: 10.2337/db16-0460
  • Radha, V., Ek, J., Anuradha, S., Hansen, T., Pedersen, O. ve Mohan, V. Identification of Novel Variants in the Hepatocyte Nuclear Factor-1 Gene in South Indian Patients with Maturity Onset Diabetes of Young. J Clin Endocrinol Metab, 94, (2009), 1959–1965.
  • Zhang, M., Zhou, J.J., Cui, W., Li, Y., Yang, P., Chen, X. ve ark. Molecular and phenotypic characteristics of maturity-onset diabetes of the young compared with early onset type 2 diabetes in China. Journal of Diabetes 7, (2015), 858–863.
  • Köse, T. Türk Popülasyonunda HNF1A Gen Mutasyonlarının Araştırılması. DETAE Genç Araştırıcılar Toplantısı. Kongre kitapçığı, (2015), sf 27.
  • Ranade S.S., Deobagkar, D.N. ve Deobagkar, D. D. Identification of I27L polymorphism in the HNF1A gene in Western Indian population with late onset of diabetes. International Journal of Diabetes in Developing Countries, 30(4), (2010), 226-229.
  • Bonatto, N., Nogaroto, V., Svidnicki, P.V., Milléo, F.Q., Grassiolli, S., Almeida, M.C., ve ark. Variants of the HNF1A gene: A molecular approach concerning diabetic patients from southern Brazil. Genetics and Molecular Biology, 35(4), (2012), 737-740.
  • Moghbeli, M., Naghibzadeh, B., Ghahraman, M., Fatemi, S., Taghavi, M., Vakili, R. ve ark. Mutations in HNF1A Gene are not a Common Cause of Familial Young-Onset Diabetes in Iran. Ind J Clin Biochem, 33(1), (2018), 91–95.
  • Yang, Y., Zhou, T.C., Liu, Y.Y., Li, X., Wang, W.X., Irwin, D.M. ve Zhang, Y.P. Identification of HNF4A Mutation p.T130I and HNF1A Mutations p.I27L and p.S487N in a Han Chinese Family with Early-Onset Maternally Inherited Type 2 Diabetes. J Diabetes Res, (2016), Article ID: 3582616. doi:10.1155/2016/3582616
Year 2018, Issue: 1, 21 - 32, 30.09.2018

Abstract

References

  • McDonald, T.J. ve Ellard, S. Maturity onset diabetes of the young: identification and diagnosis. Annals of Clinical Biochemistry, 50(5), (2013), 403–415.
  • Nakhla, M. ve Polychronakos, C. Monogenic and Other Unusual Causes of Diabetes Mellitus. Pediatric Clinics of North America, 52, (2005), 1637– 1650.
  • Velho, G. ve Froguel, P. Genetic, metabolic and clinical characteristics of maturity onset diabetes of the young. European Journal of Endocrinology, 138, (1998), 233±239.
  • Yılmaz-Ağladıoğlu, S., Aycan, Z., Çetinkaya, S., Baş, V.N., Önder, A., Peltek-Kendirci, H.N. ve ark. Maturity onset diabetes of youth (MODY) in Turkish children: sequence analysis of 11 causative genes by next generation sequencing. J Pediatr Endocrinol Metab. 29(4), (2016), 487–496.
  • Atabek, M.E. ve Kurtoglu, S. Gençlerin Erişkin Başlangıçlı Diabeti. Turkish Journal Of Medical Sciences, 24, (2004), 167-172.
  • Javadi, M., Rafatpanah, H., Taghavi, S. M., Tavakolafshari, J., Ganjali, R., Valizadeh, N. ve ark. Analysis of the glucokinase gene in Iranian families with maturity onset diabetes of the young. Journal of Diabetes Mellitus, 03(04), (2013), 192-198. doi:10.4236/jdm.2013.34029
  • Covantev, S., Chiriac, A., Perciuleac, L. ve Zozina, V. Maturity onset diabetes of the young: Diagnosis and treatment options, 5(4), (2016), e0402 doi: 10.15275/rusomj.2016.0402
  • Kahn, C.R., Weir, G.C., King, G.L., Moses, A.C., Smith, R.J. ve Jacobson, A.M. Joslin’s Diabetes mellitus. 14. Baskı. (2005). Chapter 22: Genetics of Type 2 Diabetes Lippincott Williams and Wilkins, sf 371-392.
  • Kim, S.H. Maturity-onset diabetes of the young: what do cli¬nicians need to know? Diabetes Metab J. 39, (2015), 468-77.
  • Prudente, S., Jungtrakoon, P., Marucci, A., Ludovico, O., Buranasupkajorn, P., Mazza, T, ve ark. Loss-of-Function Mutations in APPL1 in Familial Diabetes Mellitus. Am J Hum Genet, 97(1), (2015), 177-185. doi:10.1016/j.ajhg.2015.05.011
  • Ovsyannikova, A.K., Rymar, O.D., Shakhtshneider, E.V., Klimontov, V.V., Koroleva, E.A., Myakina, N.E. ve Voevoda, M.I. ABCC8-Related Maturity-Onset Diabetes of the Young (MODY12): Clinical Features and Treatment Perspective. Diabetes Ther, 7(3), (2016), 591-600. doi:10.1007/s13300-016-0192-9
  • Colclough, K., Bellanne-Chantelot, C., Saint-Martin, C., Flanagan, S.E., ve Ellard, S. Mutations in the Genes Encoding the Transcription Factors Hepatocyte Nuclear Factor 1 Alpha and 4 Alpha in Maturity-Onset Diabetes of the Young and Hyperinsulinemic Hypoglycemia. Hum Mutat, 34, (2013), 669–685.
  • Negahdar, M., Aukrust,I., Molnes, J., Solheim, M.H., Johansson, B.B., Sagen, J.V. ve ark. GCK-MODY diabetes as a protein misfolding disease: The mutation R275C promotes protein misfolding, self-association and cellular degradation. Biochim Biophys Acta. Nov; 1822(11), (2012), 1705-15. doi: 10.1016/j.bbadis.2012.07.005.
  • Hattersley, A.T ve Patel, K.A. Precision diabetes: learning from monogenic diabetes. Diabetologia, 60, (2017), 769-777. DOI 10.1007/s00125-017-4226-2
  • Gardner, D.S. ve Tai, E.S. Clinical features and treatment of maturity onset diabetes of the young (MODY). Diabetes Metab Syndr Obes, 5, (2012), 101-108. doi:10.2147/DMSO.S23353
  • Juszczak, A. ve Owen, K. Identifying subtypes of monogenicdiabetes. Diabetes Manage, 4(1), (2014), 49–61.
  • Kleinberger, J.W. ve Pollin, T.I. Undiagnosed MODY: Time for Action. Curr Diab Rep, 15(12), (2015), 110. doi:10.1007/s11892-015-0681-7
  • Beijers, H. J., Losekoot, M., Odink, R. J. ve Bravenboer, B. Hepatocyte nuclear factor (HNF)1A and HNF4A substitution occurring simultaneously in a family with maturity-onset diabetes of the young. Diabet Med, 26(11), (2009), 1172-1174. doi:10.1111/j.1464-5491.2009.02855.x
  • Forlani, G., Zucchini, S., Di Rocco, A., Di Luzio, R., Scipione, M., Marasco, E. ve ark. Double heterozygous mutations involving both HNF1A/MODY3 and HNF4A/MODY1 genes: a case report. Diabetes Care, 33(11), (2010), 2336-2338. doi:10.2337/dc10-0561
  • Lopez-Garrido, M.P., Herranz-Antolin, S., Alija-Merillas, M.J., Giralt, P. ve Escribano, J. Co-inheritance of HNF1a and GCK mutations in a family with maturity-onset diabetes of the young (MODY): implications for genetic testing. Clin Endocrinol (Oxf), 79(3), (2013), 342-347. doi:10.1111/cen.12050
  • Estalella, I., Rica, I., Perez de Nanclares, G., Bilbao, J.R., Vazquez, J.A., San Pedro, J.I. ve ark. Mutations in GCK and HNF-1alpha explain the majority of cases with clinical diagnosis of MODY in Spain. Clin Endocrinol (Oxf), 67(4), (2007), 538-546. doi:10.1111/j.1365-2265.2007.02921.x
  • Ellard, S. Hepatocyte nuclear factor 1 alpha (HNF-1-alpha) mutations in maturity-onset diabetes of the young. Hum. Mutat, 16, (2000), 377-385.
  • Gragnoli, C., Lindner, T., Cockburn, B.N., Kaisaki, P.J., Gragnoli, F. veMarozzi, G. ve ark. Maturity-Onset Diabetes of the Young Due to a Mutation in the Hepatocyte Nuclear Factor-4aBinding Site in the Promoter of the HepatocyteNuclear Factor-la Gene. Diabetes, 46, (1997), 1648-1651.
  • Bonnycastle, L.L., Willer, C.J., Conneely, K.N., Jackson, A.U. Burril, C.P., Watanabe, R.M., ve ark. Common Variants in Maturity-Onset Diabetes of the Young Genes Contribute to Risk of Type 2 Diabetes in Finns. Diabetes, 55, (2006), 2534–2540.
  • Holmkvist, J., Almgren, P., Lyssenko, V., Lindgren, C.M., Eriksson, K.F., Isomaa, B. ve ark. Common Variants in Maturity-Onset Diabetes of the Young Genes and Future Risk of Type 2 Diabetes. Diabetes, 7, (2008), 1738–1744.
  • Pruhova, S., Ek, J., Lebl, J., Sumnik, Z., Saudek, F., Andel, M., ve ark. Genetic epidemiology of MODY in the Czech republic: new mutations in the MODY genes HNF-4alpha, GCK and HNF-1alpha. Diabetologia, 46(2), (2003), 291-295. doi:10.1007/s00125-002-1010-7
  • Ryffel, G.U. Mutations in the human genes encoding the transcription factors of the hepatocyte nuclear factor (HNF)1 and HNF4 families: functional and pathological consequences. Journal of Molecular Endocrinology, 27, (2001), 11–29.
  • Morita, K.,Saruwatari, T., Tanaka, T., Oniki, K., Kajiwara, A., Otakeb, K.K., Ogatab, Y. ve ark. Associations between the common HNF1A gene variant p.I27L (rs1169288) and risk of type 2 diabetes mellitus are influenced by weight. Diabetes & Metabolism, (2014), 4 pages.
  • Giuffrida, F.M.A., Furuzawa, G.K., Kasamatsu, T.S., Oliveira, M.M., Reis, A.F. ve Dib S.A. HNF1A gene polymorphisms and cardiovascular risk factors in individuals with late-onset autosomal dominant diabetes: a cross-sectional study. Cardiovascular Diabetology, 8(28), (2009), 9 pages. doi:10.1186/1475-2840-8-28
  • Eide, S.A., Raeder, H., Johansson, S., Midthjell, K., Sovik, O., Njolstad, P.R.ve ark. Prevalence of HNF1A (MODY3) mutations in a Norwegian population (the HUNT2 Study). Diabet. Med. 25, (2008), 775–781. DOI: 10.1111/j.1464-5491.2008.02459.x
  • Reiner, A.P., Barber, M.J., Guan, Y., Ridker, P.M., Lange, L.A., Chasman, D.I., ve ark. Polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are associated with C-reactive protein. Am J Hum Genet., 82(5), (2012), 1193-201. doi: 10.1016/j.ajhg.2008.03.017.
  • Najmi, L.A., Aukrust, I., Flannick, J., Molnes, J., Burtt, N., Molven, A. ve ark. Functional Investigations of HNF1A Identify Rare Variants as Risk Factors for Type 2 Diabetes in the General Population. Diabetes, 66, (2017), 335–346. DOI: 10.2337/db16-0460
  • Radha, V., Ek, J., Anuradha, S., Hansen, T., Pedersen, O. ve Mohan, V. Identification of Novel Variants in the Hepatocyte Nuclear Factor-1 Gene in South Indian Patients with Maturity Onset Diabetes of Young. J Clin Endocrinol Metab, 94, (2009), 1959–1965.
  • Zhang, M., Zhou, J.J., Cui, W., Li, Y., Yang, P., Chen, X. ve ark. Molecular and phenotypic characteristics of maturity-onset diabetes of the young compared with early onset type 2 diabetes in China. Journal of Diabetes 7, (2015), 858–863.
  • Köse, T. Türk Popülasyonunda HNF1A Gen Mutasyonlarının Araştırılması. DETAE Genç Araştırıcılar Toplantısı. Kongre kitapçığı, (2015), sf 27.
  • Ranade S.S., Deobagkar, D.N. ve Deobagkar, D. D. Identification of I27L polymorphism in the HNF1A gene in Western Indian population with late onset of diabetes. International Journal of Diabetes in Developing Countries, 30(4), (2010), 226-229.
  • Bonatto, N., Nogaroto, V., Svidnicki, P.V., Milléo, F.Q., Grassiolli, S., Almeida, M.C., ve ark. Variants of the HNF1A gene: A molecular approach concerning diabetic patients from southern Brazil. Genetics and Molecular Biology, 35(4), (2012), 737-740.
  • Moghbeli, M., Naghibzadeh, B., Ghahraman, M., Fatemi, S., Taghavi, M., Vakili, R. ve ark. Mutations in HNF1A Gene are not a Common Cause of Familial Young-Onset Diabetes in Iran. Ind J Clin Biochem, 33(1), (2018), 91–95.
  • Yang, Y., Zhou, T.C., Liu, Y.Y., Li, X., Wang, W.X., Irwin, D.M. ve Zhang, Y.P. Identification of HNF4A Mutation p.T130I and HNF1A Mutations p.I27L and p.S487N in a Han Chinese Family with Early-Onset Maternally Inherited Type 2 Diabetes. J Diabetes Res, (2016), Article ID: 3582616. doi:10.1155/2016/3582616
There are 39 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

DENİZ Kanca Demirci 0000-0002-7416-058X

Hülya Yılmaz Aydoğan

Nurdan Gül

Yıldız Tütüncü This is me

Oğuz Öztürk

İlhan Satman

Publication Date September 30, 2018
Published in Issue Year 2018 Issue: 1

Cite

APA Kanca Demirci, D., Yılmaz Aydoğan, H., Gül, N., Tütüncü, Y., et al. (2018). HNF1A Geni rs1169288 (A>C) Mutasyonunun MODY3 Üzerine Etkisinin Araştırılması. Haliç Üniversitesi Fen Bilimleri Dergisi, 1(1), 21-32.

T. C. Haliç University Journal of Science