Genetic determinants of type 2 diabetes mellitus

被引:43
作者
Busch, CP [1 ]
Hegele, RA [1 ]
机构
[1] John P Robarts Res Inst, Blackburn Cardiovasc Genet Lab, London, ON N6A 5K8, Canada
关键词
complex disease; diabetes; insulin resistance; metabolic syndrome; polygenic trait;
D O I
10.1034/j.1399-0004.2001.600401.x
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Type 2 diabetes refers to a group of disparate metabolic diseases, which are typically characterized by insulin resistance in peripheral tissues, together with impaired insulin secretion from pancreatic beta -cells. The complexity of type 2 diabetes is related to factors such as genetic heterogeneity, interactions between genes, and the modulating role played by the environment. Recent progress has included defining the molecular basis of monogenic forms of type 2 diabetes, such as familial partial lipodystrophy and the subtypes of maturity-onset diabetes of the young (MODY), and also the identification of chromosomal regions that may harbor type 2 diabetes susceptibility genes. Many common variants in functional and positional candidate genes, including ADRB3, PPARG, ENPP1, and CAPN10, have also been studied for their possible role as determinants of type 2 diabetes, with varying levels of agreement between studies. The availability of a relatively complete sequence of the human genome will increase the amount of genetic information that can be used to evaluate hypotheses for the genetic basis of type 2 diabetes. To make sense of human type 2 diabetes in the post-genomic era, it is essential to have well-defined phenotypes in addition to sufficient numbers of individuals with the appropriate pedigree structure from families and/or communities.
引用
收藏
页码:243 / 254
页数:12
相关论文
共 113 条
[71]   Diabetes, defective pancreatic morphogenesis, and abnormal enteroendocrine differentiation in BETA2/NeuroD-deficient mice [J].
Naya, FJ ;
Huang, HP ;
Qiu, YH ;
Mutoh, H ;
DeMayo, FJ ;
Leiter, AB ;
Tsai, MJ .
GENES & DEVELOPMENT, 1997, 11 (18) :2323-2334
[72]   A gene conferring susceptibility to type 2 diabetes in conjunction with obesity is located on chromosome 18p11 [J].
Parker, A ;
Meyer, J ;
Lewitzky, S ;
Rennich, JS ;
Chan, GY ;
Thomas, JD ;
Orho-Melander, M ;
Lehtovirta, M ;
Forsblom, C ;
Hyrkkö, A ;
Carlsson, M ;
Lindgren, C ;
Groop, LC .
DIABETES, 2001, 50 (03) :675-680
[73]   A genome scan for type 2 diabetes susceptibility loci in a genetically isolated population [J].
Permutt, MA ;
Wasson, JC ;
Suarez, BK ;
Lin, J ;
Thomas, J ;
Meyer, J ;
Lewitzky, S ;
Rennich, JS ;
Parker, A ;
DuPrat, L ;
Maruti, S ;
Chayen, S ;
Glaser, B .
DIABETES, 2001, 50 (03) :681-685
[74]   The Pro12Ala substitution in the peroxisome proliferator activated receptor gamma 2 is associated with an insulin-sensitive phenotype in families with familial combined hyperlipidemia and in nondiabetic elderly subjects with dyslipidemia [J].
Pihlajamäki, J ;
Miettinen, R ;
Valve, R ;
Karjalainen, L ;
Mykkänen, L ;
Kuusisto, J ;
Deeb, S ;
Auwerx, J ;
Laakso, M .
ATHEROSCLEROSIS, 2000, 151 (02) :567-574
[75]   A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance [J].
Pizzuti, A ;
Frittitta, L ;
Argiolas, A ;
Baratta, R ;
Goldfine, ID ;
Bozzali, M ;
Ercolino, T ;
Scarlato, G ;
Iacoviello, L ;
Vigneri, R ;
Tassi, V ;
Trischitta, V .
DIABETES, 1999, 48 (09) :1881-1884
[76]   Non-insulin-dependent diabetes mellitus - A genetically programmed failure of the beta cell to compensate for insulin resistance [J].
Polonsky, KS ;
Sturis, J ;
Bell, GI .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 334 (12) :777-783
[77]   THE BETA-CELL IN DIABETES - FROM MOLECULAR-GENETICS TO CLINICAL RESEARCH [J].
POLONSKY, KS .
DIABETES, 1995, 44 (06) :705-717
[78]   The insulin gene is transcribed in the human thymus and transcription levels correlate with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes [J].
Pugliese, A ;
Zeller, M ;
Fernandez, A ;
Zalcberg, LJ ;
Bartlett, RJ ;
Ricordi, C ;
Pietropaolo, M ;
Eisenbarth, GS ;
Bennett, ST ;
Patel, DD .
NATURE GENETICS, 1997, 15 (03) :293-297
[79]   The natural history of type 2 diabetes - Implications for clinical practice [J].
Ramlo-Halsted, BA ;
Edelman, SV .
PRIMARY CARE, 1999, 26 (04) :771-+
[80]   The K121Q variant of the human PC-1 gene is not associated with insulin resistance or type 2 diabetes among Danish Caucasians [J].
Rasmussen, SK ;
Urhammer, SA ;
Pizzuti, A ;
Echwald, SM ;
Ekstrom, CT ;
Hansen, L ;
Hansen, T ;
Borch-Johnsen, K ;
Frittitta, L ;
Trischitta, V ;
Pedersen, O .
DIABETES, 2000, 49 (09) :1608-1611