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Analysis of the glucokinase gene in Iranian families with maturity onset diabetes of the young

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DOI: 10.4236/jdm.2013.34029    3,350 Downloads   5,051 Views   Citations

ABSTRACT

Non insulin dependent diabetes mellitus (NIDDM) as a most common form of diabetes is a major public health problem; there is a subgroup of NIDDM patients who develop the disease at an early age and show a dominant mode of inheritance. This type is nominates Maturity onset diabetes of the young (MODY). The prevalence of MODY is difficult to access, and patients with MODY genes mutations are often identified during routine screening for other purposes. MODY2 was linked to glucokinase gene (GCK) mutations, and accounted for 8% to 56% of MODY, with the highest prevalence found in the southern Europe. The aim of this study was to examine the prevalence and nature of mutations in GCK gene in Iranian paients. We have screened GCK mutations by polymerase chain reaction (PCR); single stranded conformation polymorphism (SSCP) technique in 12 Iranian families with clinical diagnosis of MODY, included 30 patients (8 males and 22 females) and their 21 family members. PCR products with abnormal mobility in denaturing gradient gel electrophoresis (DGGE) were directly sequenced. We identified 6 novel mutations in GCK gene in Iranian families (corresponding to 36.6% prevalence). Our findings and the last study on MODY1 highlight that in addition to GCK, other MODY genes such as MODY3 and MODYX may play a significant role in diabetes characterized by monogenic autosomal dominant transmission. There is an important point that the genetic recognation can be used to pre-symptomatically identify family members at risk for developing MODY.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Javadi, M. , Rafatpanah, H. , Taghavi, S. , Tavakolafshari, J. , Ganjali, R. , Valizadeh, N. and Fatemi, S. (2013) Analysis of the glucokinase gene in Iranian families with maturity onset diabetes of the young. Journal of Diabetes Mellitus, 3, 192-198. doi: 10.4236/jdm.2013.34029.

References

[1] Fajans, S.S., Bell, G.I., Bowden, D.W., Halter, J.B. and Polonsky, K.S. (1994) Maturity onset diabetes of the young. Life Sciences, 55, 413-422. http://dx.doi.org/10.1016/0024-3205(94)90052-3
[2] Fajans, S.S., Bell, G.I. and Polonsky, K.S. (2001) Molecular mechanisms and clinical pathophysiology of maturity onset diabetes of the young. New England Journal of Medicine, 345, 971-980. http://dx.doi.org/10.1056/NEJMra002168
[3] Guazzarotti, L., Fumelli, P., Testa, I., Pecora, R., Panicari, F., Bellanne-Chantelot, C. and Bartolotta, E. (2001) Diagnosis of MODY in the offspring of parents with insulin dependent and non insulin dependent diabetes mellitus. Journal of Pediatric Endocrinology and Metabolism, 14, 611-617. http://dx.doi.org/10.1515/JPEM.2001.14.S1.611
[4] Ehtisham, S., Hattersley, A.T., Dunger, D.B. and Barrett, T.G. (2004) British Society for Paediatric Endocrinology and Diabetes Clinical Trials Group. First UK survey of paediatric type 2 diabetes and MODY. Archives of Disease in Childhood, 89, 526-529. http://dx.doi.org/10.1136/adc.2003.027821
[5] Lindner, T.H., Cockburn, B.N. and Bell, G.I. (1999) Molecular genetics of MODY in Germany. Diabetologia, 42, 121-123. http://dx.doi.org/10.1007/s001250051128
[6] Costa, A., Bescos, M., Velho, G., Chevre, J., Vidal, J., Sesmilo, G., Bellanne Chantelot, C., Froguel, P., Casamitjana, R., Rivera-Fillat, F., Gomis, R. and Conget, I. (2000) Genetic and clinical characterisation of maturity onset diabetes of the young in Spanish families. European Journal of Endocrinology, 142, 380-386. http://dx.doi.org/10.1530/eje.0.1420380
[7] Frayling, T.M., Evans, J.C., Bulman, M.P., Pearson, E., Allen, L., Owen, K., Bingham, C., Hannemann, M., Shepherd, M., Ellard, S. and Hattersley, A.T. (2001) Cell genes and diabetes: Molecular and clinical characterization of mutations in transcription factors. Diabetes, 50, S94-S100. http://dx.doi.org/10.2337/diabetes.50.2007.S94
[8] Gragnoli, C. (2001) Early onset type II diabetes mellitus in Italian families due to mutations in the genes encoding hepatic nuclear factor 1α and glucokinase. Diabetologia, 44, 1326-1329.
http://dx.doi.org/10.1007/s001250100644
[9] Barrio, R., Bellanne-Chantelot, C., Moreno, J.C., Morel, V., Calle, H., Alonso, M. and Mustieles, C. (2002) Nine novel mutations in maturity onset diabetes of the young (MODY) candidate genes in 22 Spanish families. Journal of Clinical Endocrinology & Metabolism, 87, 2532-2539. http://dx.doi.org/ 10.1210/jc.87.6.2532
[10] Pruhova, S., Ek, J., Lebl, J., Sumnik, Z., Saudek, F., Andel, M., Pedersen, O. and Hansen, T. (2003) Genetic epidemiology of MODY in the Czech Republic: New mutations in the MODY genes HNF 4α, GCK and HNF 1α. Diabetologia, 46, 291-295.
[11] Pearson, E.R., Pruhova, S., Tack, C., Johansen, A., Castleden, H., Wierzbecki, A., Clark, P.M., Pedersen, O., Lebl, J., Ellard, S., Hansen, T. and Hattersley, A.T. (2005) Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4α mutations in a large European collection. Diabetologia, 48, 878-885. http://dx.doi.org/10.1007/s00125-005-1738-y
[12] Hattersley, A.T. (1998) Maturity onset diabetes of the young: Clinical heterogeneity explained by genetic heterogeneity. Diabetic Medicine, 15, 15-24. http://dx.doi.org/10.1002/(SICI)1096-9136(199801)15:1<15::AID-DIA562>3.0.CO;2-M
[13] Johansen, A., J. Ek, Mortensen, H.B., Pedersen, O. and Hansen, T. (2005) Half of clinically defined maturity onset diabetes of the young patients in Denmark do not have mutations in HNF 4α, GCK and TCF1. The Journal of Clinical Endocrinology and Metabolism, 90, 4607-4614. http://dx.doi.org/ 10.1210/jc.2005-0196
[14] Stoffel, M., Froguel, P., Takeda, J., Zouali, H., Vionnet, N., Nishi, S., Weber, I.T., Harrison, R.W., Pilkis, S.J., Lesage, S., Vaxillaire, M., Velho, G., Sun, F., Iris, F., Passa, P., Cohen, D. and Bell, G.I. (1992) Human glucokinase gene: Isolation, characterization, and identification of two missense mutations linked to early onset non insulindependent (type 2) diabetes mellitus. Proceedings of the National Academy of Sciences of the United States of America, 89, 7698-7702. http://dx.doi.org/10.1073/ pnas.89.16.7698
[15] Shimada, F, Makino, H., Hashimoto, N., Taira, M., Seino, S., Bell, G.I., Kanatsuka, A. and Yoshida, S. (1993) Type 2 (non insulin dependent) diabetes mellitus associated with a mutation of the glucokinase gene in a Japanese family. Diabetologia, 36, 433-437. http://dx.doi.org/10.1007/ BF00402280
[16] Matschinsky, F., Liang, Y., Kesavan, P., Wang, L., Froguel, P., Velho, G., Cohen, D., Permutt, M.A., Tanizawa, Y., Jetton, T.L., Niswender, K. and Magnuson, M.A. (1993) Glucokinase as pancreatic beta cell glucose sensor and diabetes gene. Journal of Clinical Investigation, 92, 2092-2098. http://dx.doi.org/10.1172/JCI116809
[17] Stoffel, M., Bell, K.L., Blackburn, C.L., Powell, K.L., Seo, T.S., Takeda, J., Vionnet, N., Xiang, K.S., Gidh-Jain, M., Pilkis, S.J., Ober, C. and Bell, G.I. (1993) Identification of glucokinase mutations in subjects with gestational diabetes mellitus. Diabetes, 42, 937-940. http://dx.doi.org/10.2337/diab.42.6.937
[18] Froguel, P., Zouali, H., Vionnet, N., Velho, G., Vaxillaire, M., Sun, F., Lesage, S., Stoffel, M., Takeda, J., Passa, P., Permutt, M.A., Beckmann, J.S., Bell, G.I. and Cohen, D. (1993) Familial hyperglycemia due to mutations in glucokinase: Definition of a subtype of diabetes mellitus. New England Journal of Medicine, 328, 697-702. http://dx.doi.org/10.1056/NEJM199303113281005
[19] Zouali, H., Vaxillaire, M., Lesage, S., Sun, F., Velho, G., Vionnet, N., Chiu, K., Passa, P., Permutt, A., Demenais, F., Cohen, D., Beckmann, J.S. and Froguel, P. (1993) Linkage analysis and molecular scanning of glucokinase gene in NIDDM families. Diabetes, 42, 1238-1245. http://dx.doi.org/ 10.2337/diab.42.9.1238
[20] Hager, J., Blanche, H., Sun, F., Vaxillaire, N.V., Poller, W., Cohen, D., Czernichow, P., Velho, G., Robert, J.J., Cohen, N. and Froguel, P. (1994) Six mutations in the glucokinase gene identified in MODY by using a nonradioactive sensitive screening technique. Diabetes, 43, 730-733. http://dx.doi.org/ 10.2337/diab.43.5.730
[21] Velho, G., Blanche, H., Vaxillaire, M., Bellanne-Chantelot, C., Pardini, V.C., Timsit, J., Passa, P., Deschamps, I., Robert, J.J., Weber, I.T., Marotta, D., Pilkis, S.J., Lipkind, G.M., Bell, G.I. and Froguel, P. (1997) Identification of 14 new glucokinase mutations and description of the clinical profile of 42 MODY2 families. Diabetologia, 40, 217-224. http://dx.doi.org/10.1007/s001250050666
[22] Velho, G., Froguel, P., Clement, K., Pueyo, M.E., Rakotoambinina, B., Zouali, H., Passa, P., Cohen, D. and Robert, J.J. (1992) Primary pancreatic beta cell secretory defect caused by mutations in glucokinase gene in kindreds of maturity onset diabetes of the young. Lancet, 340, 444-448. http://dx.doi.org/10.1016/0140-6736(92)91768-4
[23] Byrne, M.M., Sturis, J., Clement, K., Vionnet, N., Pueyo, M.E., Stoffel, M., Takeda, J., Passa, P., Cohen, D., Bell, G.I., Velho, G., Froguel, P. and Polonsky, K.S. (1994) Insulin secretory abnormalities in subjects with hyperglycemia due to glucokinase mutations. Journal of Clinical Investigation, 93, 1120-1130. http://dx.doi.org/10.1172/JCI117064
[24] Velho, G., Petersen, K.F., Perseghin, G., Hwang, J.H., Rothman, D.L., Pueyo, M.E., Cline, G.W., Froguel, P. and Shulman, G.I. (1996) Impaired hepatic glycogen synthesis in glucokinase deficient (MODY2) subjects. Journal of Clinical Investigation, 98, 1755-1761. http://dx.doi.org/10.1172/ JCI118974
[25] Pearson, E.R., Velho, G., Clark, P., Stride, A., Shepherd, M., Frayling, T.M., Bulman, M.P., Ellard, S., Froguel, P. and Hattersley, A. (2001) β cell genes and diabetes: Quantitative and qualitative differences in the pathophysiology of hepatic nuclear factor 1α and glucokinase mutations. Diabetes, 50, S101-S107. http://dx.doi.org/10.2337/diabetes.50.2007.S101
[26] Rose, C.S., Ek, J., Urhammer, S.A., Glumer, C., Borch-Johnsen, K., Jorgensen, T., Pedersen, O. and Hansen, T. (2005) A-30G>A Polymorphism of the β cell specific Glucokinase promoter associates with Hyperglycemia in the general population of whites. Diabetes, 54, 3026-3031. http://dx.doi.org/ 10.2337/diabetes.54.10.3026
[27] Taghavi, S.M., Fatemi, S.S., Rafatpanah, H., Ganjali, R., Tavakolafshari, J. and Valizadeh, N. (2009) Mutations in the coding regions of the hepatocyte nuclear factor 4 alpha in Iranian families with maturity onset diabetes of the young. Cardiovascular Diabetology, 8, 63. http://dx.doi.org/ 10.1186/1475-2840-8-63
[28] del Bosque-Plata, L., Garcia-Garcia, E., Ramirez-Jimenez, S., Cabello-Villegas, J., Riba, L., Gomez-Leon, A., Vega-Hernandez, G., Altamirano-Bustamante, N., Calzada-Leon, R., Robles-Valdes, C., Mendoza-Morfin, F., Curiel-Perez, O. and Tusie Luna, M.T. (1997) Analysis of the Glucokinase gene in Mexican families displaying early onset non insulin dependent diabetes mellitus including MODY families. American Journal of Medical Genetics, 72, 387-393. http://dx.doi.org/10.1002/(SICI)1096-8628(19971112)72:4<387::AID-AJMG3>3.0.CO;2-O
[29] Barrio, R., Bellanne Chantelot, C., Moreno, J.C., Morel, V., Calle, H., Alonso, M. and Mustieles, C. (2002) Nine novel mutations in Maturity Onset Diabetes of the Young (MODY) candidate genes in 22 Spanish families. The Journal of Clinical Endocrionology and Metabolism, 8, 2532-2539.
http://dx.doi.org/10.1210/jc.87.6.2532
[30] Doria, A. and Plengvidhya, N. (2000) Recent advances in the genetics of maturity onset diabetes of the young and others forms of autosomal dominant diabetes. Current Opinion in Endocrinology and Diabetes, 7, 203-210.
[31] Froguel, P.H., Vaxillaire, M., Sun, F., Velho, G., Zouali, H., Butel, M.O., Lesage, S., Vionnet, N., Clement, K., Fougerousse, F., Tanizawa, Y., Weissenbach, J., Beckmann, S., Lathrop, G.M., Passa, P.H., Permutt, M. and Cohen, D. (1992) The glucokinase locus on chromosome 7p closely linked to early onset non insulin dependent diabetes mellitus. Nature, 356, 162-164. http://dx.doi.org/ 10.1038/356162a0
[32] Matschinsky, F.M. (1990) Glucokinase as glucose sensor and metabolic signal generator in pancreatic β cells and hepatocytes. Diabetes, 39, 647-652. http://dx.doi.org/10.2337/diab.39.6.647
[33] Postic, C., Shiota, M., Niswender, K.D., Jetton, T.L., Chen, Y., Moates, J.M., Shelton, K.D., Lindner, J., Cherrington, A.D. and Magnuson, M.A. (1999) Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic β cell specific gene knock out using Cre recombinase. Journal of Biological Chemistry, 274, 305-315. http://dx.doi.org/10.1074/jbc.274.1.305
[34] Massa, O., Meschi, F., Cuesta-Munoz, A., Caumo, A., Cerutti, F., Toni, S., Cherubini, V., Guazzarotti, L., Sulli, N., Matschinsky, F.M., Lorini, R., Iafusco, D. and Barbetti, F. (2001) High prevalence of glucokinase mutations in Italian children with MODY. Influence on glucose tolerance, first phase insulin response, insulin sensitivity and BMI. Diabetologia, 44, 898-905. http://dx.doi.org/10.1007/ s001250100530
[35] Beards, F., Frayling, T., Bulman, M., Horikawa, Y., Allen, L., Appleton, M., Bell, G.I., Ellard, S. and Hattersley, A.T.M. (1998) Mutations in hepatocyte nuclear factor 4α are not a common cause of maturity onset diabetes of the young in the UK. Diabetes, 47, 1152-1154. http://dx.doi.org/ 10.2337/diabetes.47.7.1152
[36] Lehto, M. (1999) High frequency of mutations in MODY and mitochondrial genes in Scandinavian patients with familial early onset diabetes. Diabetologia, 42, 1131-1137. http://dx.doi.org/10.1007/ s001250051281
[37] Froguel, P. (1998) Insulin promoter factor 1 gene is not a major cause of maturity onset diabetes of the young in French Caucasians. Diabetes, 47, 843-844. http://dx.doi.org/10.2337/diabetes. 47.5.843
[38] Frayling, T.M., Lindgren, C.M., Chevre, J.C., Menzel, S., Wishart, M., Benmezroua, Y., Brown, A., Evans, J.C., Subba Rao, P., Dina, C., Lecoeur, C., Kanninen, T., Almgren, P., Bulman, M.P., Wang, Y., Mills, J., Wright-Pascoe, R., Mahtani, M.M., Prisco, F., Costa, A., Cognet, I., Hansen, T., Pedersen, O., Ellard, S., Tuomi, T., Groop, L.C., Froguel, P., Hattersley, A.T. and Vaxillaire, M. (2003) A genome wide scan in families with maturity onset diabetes of the young: Evidence further genetic heterogeneity. Diabetes, 52, 872-881. http://dx.doi.org/10.2337/diabetes.52.3.872

  
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