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2008 | 3 | 1 | 1-7
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Genetic effects, gene-lifestyle interactions, and type 2 diabetes

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Type 2 diabetes has become a major public health challenge worldwide. It is now widely accepted that genetic components affect the development of type 2 diabetes, in concert with environmental factors such as lifestyle and diet. Traditional linkage mapping, positional cloning, and candidate gene-based association studies have identified a few genetic variants in genes such as TCF7L2, PPARG, and KCNJ11 that are reproducibly related to the risk of type 2 diabetes. To date, about ten genome-wide association (GWA) studies have been published. These studies discovered new susceptibility genes for type 2 diabetes and provide novel insight into the diabetes etiology. In addition, data especially from lifestyle intervention trials display promising evidence that the genetic variants may interact with changes of dietary habit and physical activity in predisposing to type 2 diabetes. The gene-lifestyle interactions merit extensive exploration in large, prospective studies. The findings from these areas will substantially improve the prediction and prevention of type 2 diabetes.
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1 - 3 - 2008
1 - 3 - 2008
  • Departments of Nutrition and Epidemiology, Harvard School of Public Health, and Channing Laboratory, Boston, Massachusetts, 02115, USA
  • [1] Wild S., Roglic G., Green A., Sicree R., King H., Global prevalence of diabetes: estimates for the year 2000 and projections for 2030, Diabetes Care, 2004, 27, 1047–1053[Crossref]
  • [2] Sladek R., Rocheleau G., Rung J., Dina C., Shen L., Serre D., et al., A genome-wide association study identifies novel risk loci for type 2 diabetes, Nature, 2007, 445, 881–885[Crossref]
  • [3] Scott L.J., Mohlke K.L., Bonnycastle L.L., Willer C.J., Li Y., Duren W.L., et al., A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants, Science, 2007, 316, 1341–1345[Crossref]
  • [4] Salonen J.T., Uimari P., Aalto J.M., Pirskanen M., Kaikkonen J., Todorova B., et al., Type 2 diabetes whole-genome association study in four populations: the DiaGen consortium, Am. J. Hum. Genet. 2007, 81, 338–345[Crossref]
  • [5] Zeggini E., Weedon M.N., Lindgren C.M., Frayling T.M., Elliott K.S., Lango H., et al., Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes, Science, 2007, 316, 1336–1341[Crossref]
  • [6] Hunter D.J., Gene-environment interactions in human diseases, Nat. Rev. Genet., 2005, 6, 287–298[Crossref]
  • [7] Knowler W.C., Pettitt D.J., Savage P.J., Bennett P.H., Diabetes incidence in Pima indians: contributions of obesity and parental diabetes, Am. J. Epidemiol., 1981, 113, 144–156
  • [8] Harris M.I., Hadden W.C., Knowler W.C., Bennett P.H., Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in U.S. population aged 20–74 yr., Diabetes, 1987, 36, 523–534[Crossref]
  • [9] Mitchell B.D., Valdez R., Hazuda H.P., Haffner S.M., Monterrosa A., Stern M.P., Differences in the prevalence of diabetes and impaired glucose tolerance according to maternal or paternal history of diabetes, Diabetes Care, 1993, 16, 1262–1267[Crossref]
  • [10] Thomas F., Balkau B., Vauzelle-Kervroedan F., Papoz L., Maternal effect and familial aggregation in NIDDM. The CODIAB Study. CODIAB-INSERMZENECA Study Group, Diabetes, 1994, 43, 63–67[Crossref]
  • [11] De Silva S.N., Weerasuriya N., De Alwis N.M., De Silva M.W., Fernando D.J., Excess maternal transmission and familial aggregation of Type 2 diabetes in Sri Lanka. Diabetes Res. Clin. Pract. 2002, 58, 173–177[Crossref]
  • [12] Arfa I., Abid A., Malouche D., Ben Alaya N., Azegue T.R., Mannai I., et al., Familial aggregation and excess maternal transmission of type 2 diabetes in Tunisia, Postgrad. Med. J., 2007, 83, 348–351[Crossref]
  • [13] Viswanathan M., McCarthy M.I., Snehalatha C., Hitman G.A., Ramachandran A., Familial aggregation of type 2 (non-insulin-dependent) diabetes mellitus in south India; absence of excess maternal transmission, Diabet. Med., 1996, 13, 232–237<232::AID-DIA27>3.0.CO;2-7[Crossref]
  • [14] Valdez R., Yoon P.W., Liu T., Khoury M.J., Family history and prevalence of diabetes in the US population: 6-year results from the National Health and Nutrition Examination Survey (NHANES, 1999 2004), Diabetes, 2007, (in press)
  • [15] Newman B., Selby J.V., King M.C., Slemenda C., Fabsitz R., Friedman G.D., Concordance for type 2 (non-insulin-dependent) diabetes mellitus in male twins, Diabetologia, 1987, 30, 763–768[Crossref]
  • [16] Barnett A.H., Eff C., Leslie R.D., Pyke D.A., Diabetes in identical twins. A study of 200 pairs, Diabetologia, 1981, 20, 87–93[Crossref]
  • [17] Gottlieb M.S., Root H.F., Diabetes mellitus in twins, Diabetes, 1968, 17, 693–704 [PubMed][Crossref]
  • [18] Kaprio J., Tuomilehto J., Koskenvuo M., Romanov K., Reunanen A., Eriksson J., et al., Concordance for type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus in a population-based cohort of twins in Finland, Diabetologia, 1992, 35, 1060–1067[Crossref]
  • [19] Poulsen P, Kyvik K.O., Vaag A., Beck-Nielsen H., Heritability of type II (non-insulin-dependent) diabetes mellitus and abnormal glucose tolerance-a population-based twin study, Diabetologia, 1999, 42, 139–145[Crossref]
  • [20] Barroso I., Genetics of Type 2 diabetes, Diabet. Med., 2005, 22, 517–535[Crossref]
  • [21] Babenko A.P., Polak M., Cave H., Busiah K., Czernichow P., Scharfmann R., et al., Activating mutations in the ABCC8 gene in neonatal diabetes mellitus, N. Engl. J. Med., 2006, 355, 456–466.[Crossref]
  • [22] Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J., Slingerland A.S., et al., Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes., N. Engl. J. Med., 2004, 350, 1838–1849[Crossref]
  • [23] van den Ouweland J.M., Lemkes H.H., Trembath R.C., Ross R., Velho G., Cohen D., et al., Maternally inherited diabetes and deafness is a distinct subtype of diabetes and associates with a single point mutation in the mitochondrial tRNA(Leu(UUR)) gene, Diabetes, 1994, 43, 746–751[Crossref]
  • [24] Fajans S.S., Bell G.I., Polonsky K.S., Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young, N. Engl. J. Med., 2001, 345, 971–980[Crossref]
  • [25] Collins F.S., Positional cloning: let’s not call it reverse anymore, Nat. Genet., 1992, 1, 3–6[Crossref]
  • [26] Hanis C.L., Boerwinkle E., Chakraborty R., Ellsworth D.L., Concannon P., Stirling B., et al., A genome-wide search for human non-insulindependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2, Nat. Genet., 1996, 13, 161–166[Crossref]
  • [27] Horikawa Y., Oda N., Cox N.J., Li X., Orho-Melander M., Hara M., et al., Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus, Nat. Genet., 2000, 26, 163–175[Crossref]
  • [28] Grant S.F., Thorleifsson G., Reynisdottir I., Benediktsson R., Manolescu A., Sainz J., et al., Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes, Nat. Genet., 2006, 38, 320–323[Crossref]
  • [29] Reynisdottir I., Thorleifsson G., Benediktsson R., Sigurdsson G., Emilsson V., Einarsdottir A.S., et al., Localization of a susceptibility gene for type 2 diabetes to chromosome 5q34-q35.2, Am. J. Hum. Genet., 2003, 73, 323–335[Crossref]
  • [30] Cauchi S., El Achhab Y., Choquet H., Dina C., Krempler F., Weitgasser R., et al., TCF7L2 is reproducibly associated with type 2 diabetes in various ethnic groups: a global meta-analysis, J. Mol. Med., 2007, 85, 777–782[Crossref]
  • [31] Risch N., Merikangas K., The future of genetic studies of complex human diseases, Science, 1996, 273, 1516–1517[Crossref]
  • [32] Watanabe R.M., Black M.H., Xiang A.H., Allayee H., Lawrence J.M., Buchanan T.A., Genetics of gestational diabetes mellitus and type 2 diabetes, Diabetes Care, 2007, 30, Suppl 2, S134–140[Crossref]
  • [33] Newton-Cheh C., Hirschhorn J.N., Genetic association studies of complex traits: design and analysis issues, Mutat. Res., 2005, 573, 54–69
  • [34] Ludovico O., Pellegrini F., Di Paola R., Minenna A., Mastroianno S., Cardellini M., et al., Heterogeneous effect of peroxisome proliferatoractivated receptor gamma2 Ala12 variant on type 2 diabetes risk, Obesity (Silver Spring), 2007, 15, 1076–1081[Crossref]
  • [35] Nielsen E.M., Hansen L., Carstensen B., Echwald S.M., Drivsholm T., Glumer C., et al., The E23K variant of Kir6.2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes, Diabetes, 2003, 52, 573–577[Crossref]
  • [36] Winckler W., Weedon M.N., Graham R.R., McCarroll S.A., Purcell S., Almgren P., et al., Evaluation of common variants in the six known maturity-onset diabetes of the young (MODY) genes for association with type 2 diabetes, Diabetes, 2007, 56, 685–693[Crossref]
  • [37] Gudmundsson J., Sulem P., Steinthorsdottir V., Bergthorsson J.T., Thorleifsson G., Manolescu A., et al., Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes, Nat. Genet., 2007, 39, 977–983[Crossref]
  • [38] Jorgenson E., Witte J.S., A gene-centric approach to genome-wide association studies, Nat. Rev. Genet., 2006, 7, 885–891[Crossref]
  • [39] Saxena R., Voight B.F., Lyssenko V., Burtt N.P., de Bakker P.I., Chen H., et al., Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels, Science, 2007, 316, 1331–1336[Crossref]
  • [40] Steinthorsdottir V., Thorleifsson G., Reynisdottir I., Benediktsson R., Jonsdottir T., Walters G.B., et al., A variant in CDKAL1 influences insulin response and risk of type 2 diabetes, Nat. Genet., 2007, 39, 770–775[Crossref]
  • [41] Florez J.C., Manning A.K., Dupuis J., McAteer J., Irenze K., Gianniny L., et al., A 100k Genome-Wide Association Scan for Diabetes and Related Traits in the Framingham Heart Study: Replication and Integration with Other Genome-Wide Datasets, Diabetes 2007, (in press) [Crossref]
  • [42] Rampersaud E., Damcott C.M., Fu M., Shen H., McArdle P., Shi X., et al., Identification of novel candidate genes for type 2 diabetes from a genome-wide association scan in the Old Order Amish: Evidence for replication from diabetesrelated quantitative traits and from independent populations, Diabetes, 2007, (in press) [Crossref]
  • [43] Hanson R.L., Bogardus C., Duggan D., Kobes S., Knowlton M., Infante A.M., A Search for Variants Associated with Young-Onset Type 2 Diabetes in American Indians in a 100k Genotyping Array, Diabetes, 2007, (in press) [Crossref]
  • [44] Nemoto M., Sasaki T., Deeb S.S., Fujimoto W.Y., Tajima N., Differential effect of PPARgamma2 variants in the development of type 2 diabetes between native Japanese and Japanese Americans, Diabetes Res. Clin. Pract., 2002, 57, 131–137[Crossref]
  • [45] Laaksonen D.E., Lindstrom J., Lakka T.A., Eriksson J.G., Niskanen L., Wikstrom K., et al., Physical activity in the prevention of type 2 diabetes: the Finnish diabetes prevention study, Diabetes, 2005, 54, 158–165[Crossref]
  • [46] Siitonen N., Lindstrom J., Eriksson J., Valle T.T., Hamalainen H., Ilanne-Parikka P., et al., Association between a deletion/insertion polymorphism in the alpha2B-adrenergic receptor gene and insulin secretion and Type 2 diabetes. The Finnish Diabetes Prevention Study, Diabetologia, 2004, 47, 1416–1424[Crossref]
  • [47] Lindi V.I., Uusitupa M.I., Lindstrom J., Louheranta A., Eriksson J.G., Valle T.T., et al., Association of the Pro12Ala polymorphism in the PPAR-gamma2 gene with 3-year incidence of type 2 diabetes and body weight change in the Finnish Diabetes Prevention Study, Diabetes, 2002, 51, 2581–2586[Crossref]
  • [48] Laukkanen O., Lindstrom J., Eriksson J., Valle T.T., Hamalainen H., Ilanne-Parikka P., et al., Polymorphisms in the SLC2A2 (GLUT2) gene are associated with the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study, Diabetes, 2005, 54, 2256–2260[Crossref]
  • [49] Salopuro T., Pulkkinen L., Lindstrom J., Eriksson J.G., Valle T.T., Hamalainen H., et al. Genetic variation in leptin receptor gene is associated with type 2 diabetes and body weight: The Finnish Diabetes Prevention Study, Int. J. Obes. (Lond.), 2005, 29, 1245–1251[Crossref]
  • [50] Kubaszek A., Pihlajamaki J., Komarovski V., Lindi V., Lindstrom J., Eriksson J., et al., Promoter polymorphisms of the TNF-alpha (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study, Diabetes, 2003, 52, 1872–1876[Crossref]
  • [51] Mager U., Lindi V., Lindstrom J., Eriksson J.G., Valle T.T., Hamalainen H., et al., Association of the Leu72Met polymorphism of the ghrelin gene with the risk of Type 2 diabetes in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study, Diabetes Med., 2006, 23, 685–689[Crossref]
  • [52] Florez J.C., Jablonski K.A., Bayley N., Pollin T.I., de Bakker P.I., Shuldiner A.R., et al., TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program, N. Engl. J. Med., 2006, 355, 241–250[Crossref]
  • [53] Nelson T.L., Fingerlin T.E., Moss L.K., Barmada M.M., Ferrell R.E., Norris J.M., Association of the peroxisome proliferator-activated receptor gamma gene with type 2 diabetes mellitus varies by physical activity among non-Hispanic whites from Colorado, Metabolism, 2007, 56, 388–393[Crossref]
  • [54] Soriguer F., Morcillo S., Cardona F., Rojo-Martinez G., de la Cruz Almaraz M., Ruiz de Adana Mde L., et al., Pro12Ala polymorphism of the PPARG2 gene is associated with type 2 diabetes mellitus and peripheral insulin sensitivity in a population with a high intake of oleic acid, J. Nutr., 2006, 136, 2325–2330
  • [55] Qi L., Meigs J., Manson J.E., Ma J., Hunter D., Rifai N., et al., HFE genetic variability, body iron stores, and the risk of type 2 diabetes in U.S. women, Diabetes, 2005, 54, 3567–3572[Crossref]
  • [56] Beulens J.W., Rimm E.B., Hendriks H.F., Hu F.B., Manson J.E., Hunter D.J., et al., Alcohol consumption and type 2 diabetes: influence of genetic variation in alcohol dehydrogenase, Diabetes, 2007, 56, 2388–2394[Crossref]
  • [57] Frayling T.M., Genome-wide association studies provide new insights into type 2 diabetes aetiology, Nat. Rev. Genet., 2007, 8, 657–662[Crossref]
  • [58] Bermejo J.L., Hemminki K., Gene-environment studies: any advantage over environmental studies? Carcinogenesis, 2007, 28, 1526–1532[Crossref]
  • [59] Willett W.C., Balancing life-style and genomics research for disease prevention. Science, 2002, 296, 695–698[Crossref]
  • [60] McCarroll S.A., Altshuler D.M., Copy-number variation and association studies of human disease, Nat. Genet., 2007, 39, S37–42[Crossref]
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