Melanocortin-3 receptor gene variants in a Maori kindred with obesity and early onset type 2 diabetes
作者： Jencia Wong , Don R Love , Cam Kyle , Andre Daniels , Marie White
DOI: 10.1016/S0168-8227(02)00126-2
关键词:
摘要: Abstract Genetic studies suggest a diabetes susceptibility locus on human chromosome 20, near the melanocortin receptor-3 (MC3-R) gene. We examined MC3-R as candidate gene for type 2 in 12 members of large Maori kindred with multiple affected members. The coding region was sequenced both diabetic and non-diabetic individuals. Two separate single base pair substitutions were found sequence these resulted amino acid changes, Lysine6Threonine Isoleucine81Valine. Neither variants tracked presence diabetes. Furthermore, variant wild showed similar functional coupling to adenylyl cyclase. A polymorphic marker (D20S32e) close (hMC3-R) investigated 60-member pedigree association other metabolic parameters. There an between D20S32e genotype fasting insulin ( P =0.0085) resistance index, HOMA-R =0.0042). An also HDL levels during oral glucose tolerance testing =0.0037). These associations independent BMI, age, gender Our data do not support role variations hMC3-R development this kindred, but that 20q, D20S32e, may contribute secretion action kindred.
elsevier.com
sci-hub.se 参考文章(44)
Kathleen G. Mountjoy, Cloning of the Melanocortin Receptors Humana Press, Totowa, NJ. pp. 209- 235 ,(2000) , 10.1007/978-1-59259-031-5_7
Wong M, Graham Fm, Frengley Pa, Holdaway Im, Insulin resistance with acanthosis nigricans and acral hypertrophy. The New Zealand Medical Journal. ,vol. 97, pp. 286- ,(1984)
Airu S. Chen, Donald J. Marsh, Myrna E. Trumbauer, Easter G. Frazier, Xiao-Ming Guan, Hong Yu, Charles I. Rosenblum, Aurawan Vongs, Yue Feng, Linhai Cao, Joseph M. Metzger, Alison M. Strack, Ramon E. Camacho, Theodore N. Mellin, Christian N. Nunes, William Min, Jill Fisher, Shobhna Gopal-Truter, D. Euan MacIntyre, Howard Y. Chen, Lex H.T. Van der Ploeg, Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nature Genetics. ,vol. 26, pp. 97- 102 ,(2000) , 10.1038/79254
Heiko Krude, Heike Biebermann, Werner Luck, Rüdiger Horn, Georg Brabant, Annette Grüters, Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans Nature Genetics. ,vol. 19, pp. 155- 157 ,(1998) , 10.1038/509
I. Gantz, Y. Konda, T. Tashiro, Y. Shimoto, H. Miwa, G. Munzert, S.J. Watson, J. DelValle, T. Yamada, Molecular cloning of a novel melanocortin receptor. Journal of Biological Chemistry. ,vol. 268, pp. 8246- 8250 ,(1993) , 10.1016/S0021-9258(18)53088-X
Giles S.H. Yeo, I. Sadaf Farooqi, Shiva Aminian, David J. Halsall, Richard G. Stanhope, Stephen O'Rahilly, A frameshift mutation in MC4R associated with dominantly inherited human obesity Nature Genetics. ,vol. 20, pp. 111- 112 ,(1998) , 10.1038/2404
F Desarnaud, O Labbe, D Eggerickx, G Vassart, M Parmentier, Molecular cloning, functional expression and pharmacological characterization of a mouse melanocortin receptor gene Biochemical Journal. ,vol. 299, pp. 367- 373 ,(1994) , 10.1042/BJ2990367
Helgi B. Schiöth, Philip Yook, Ruta Muceniece, Jarl E. S. Wikberg, Michael Szardenings, Chimeric melanocortin MC1 and MC3 receptors: identification of domains participating in binding of melanocyte-stimulating hormone peptides. Molecular Pharmacology. ,vol. 54, pp. 154- 161 ,(1998) , 10.1124/MOL.54.1.154
C Chen, H Okayama, High-efficiency transformation of mammalian cells by plasmid DNA. Molecular and Cellular Biology. ,vol. 7, pp. 2745- 2752 ,(1987) , 10.1128/MCB.7.8.2745
I.N. Migdalis, D. Zachariadis, K. Kalogeropoulou, C. Nounopoulos, A. Bouloukos, M. Samartzis, Metabolic Abnormalities in Offspring of NIDDM Patients with a Family History of Diabetes Mellitus Diabetic Medicine. ,vol. 13, pp. 434- 440 ,(1996) , 10.1002/(SICI)1096-9136(199605)13:5<434::AID-DIA102>3.0.CO;2-R