Background The association of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) common variants (rs4402960 and rs1470579) with type 2 diabetes (T2D) has been performed in different populations. The aim of this study was to evaluate the association of alternative variants of IGF2BP2; rs6777038, rs16860234 and rs7651090 with glutamic acid decarboxylase antibodies (GADA) negative diabetes in Malaysian Subjects. Methods/Principal Findings IGF2BP2; rs6777038, rs16860234 and rs7651090 single nucleotide polymorphisms (SNPs) were genotyped in 1107 GADA negative diabetic patients and 620 control subjects of Asian from Malaysia. The additive genetic model adjusted for age, race, gender and BMI showed that alternative variants; rs6777038, rs16860234 and rs7651090 of IGF2BP2 associated with GADA negative diabetes (OR = 1.21; 1.36; 1.35, P = 0.03; 0.0004; 0.0002, respectively). In addition, the CCG haplotype and diplotype CCG-TCG increased the risk of diabetes (OR = 1.51, P = 0.01; OR = 2.36, P = 0.009, respectively). Conclusions/Significance IGF2BP2 alternative variants were associated with GADA negative diabetes. The IGF2BP2 haplotypes and diplotypes increased the risk of diabetes in Malaysian subject.
References
[1]
IDF (2011) International Diabetes Federation Diabetes Atlas. 5th edition ed.
[2]
Turner R, Stratton I, Horton V, Manley S, Zimmet P, et al. (1997) UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. The Lancet 350: 1288–1293.
[3]
Monge L, Bruno G, Pinach S, Grassi G, Maghenzani G, et al. (2004) A clinically orientated approach increases the efficiency of screening for latent autoimmune diabetes in adults (LADA) in a large clinic-based cohort of patients with diabetes onset over 50 years. Diabet Med 21: 456–459.
[4]
Roh M-O, Jung C-H, Kim B-Y, Mok J-O, Kim C-H (2010) The prevalence and characteristics of latent autoimmune diabetes in adults (LADA) and its relation with chronic complications in a clinical department of a university hospital in Korea. Acta Diabetologica: 1–6.
[5]
Groop LC, Bottazzo GF, Doniach D (1986) Islet cell antibodies identify latent type I diabetes in patients aged 35–75 years at diagnosis. Diabetes 35: 237–241.
[6]
Stenstr?m G, Gotts?ter A, Bakhtadze E, Berger B, Sundkvist G (2005) Latent Autoimmune Diabetes in Adults. Diabetes 54: S68–S72.
[7]
Tuomi T, Carlsson A, Li H, Isomaa B, Miettinen A, et al. (1999) Clinical and genetic characteristics of type 2 diabetes with and without GAD antibodies. Diabetes 48: 150–157.
[8]
Jin W, Patti ME (2009) Genetic determinants and molecular pathways in the pathogenesis of Type 2 diabetes. Clin Sci (Lond) 116: 99–111.
[9]
Permutt MA, Wasson J, Cox N (2005) Genetic epidemiology of diabetes. The Journal of Clinical Investigation 115: 1431–1439.
[10]
Jia H, Yu L, Jiang Z, Ji Q (2011) Association between IGF2BP2 rs4402960 polymorphism and risk of type 2 diabetes mellitus: a meta-analysis. Arch Med Res 42: 361–367.
[11]
Sladek R, Rocheleau G, Rung J, Dina C, Shen L, et al. (2007) A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445: 881–885.
[12]
Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, et al. (2007) A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316: 1341–1345.
[13]
Takeuchi F, Serizawa M, Yamamoto K, Fujisawa T, Nakashima E, et al. (2009) Confirmation of multiple risk Loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population. Diabetes 58: 1690–1699.
[14]
Hinohara K, Nakajima T, Sasaoka T, Sawabe M, Lee BS, et al. (2009) Replication studies for the association of PSMA6 polymorphism with coronary artery disease in East Asian populations. J Hum Genet 54: 248–251.
[15]
Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, et al. (2007) Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316: 1331–1336.
[16]
Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, et al. (2007) Replication of Genome-Wide Association Signals in UK Samples Reveals Risk Loci for Type 2 Diabetes. Science 316: 1336–1341.
[17]
Consortium TWTCC (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447: 661–678.
[18]
Le HTT, Sorrell AM, Siddle K (2012) Two Isoforms of the mRNA Binding Protein IGF2BP2 Are Generated by Alternative Translational Initiation. PLoS ONE 7: e33140.
[19]
Rodriguez S, Eiriksdottir G, Gaunt TR, Harris TB, Launer LJ, et al. (2010) IGF2BP1, IGF2BP2 and IGF2BP3 genotype, haplotype and genetic model studies in metabolic syndrome traits and diabetes. Growth Hormone & IGF Research 20: 310–318.
[20]
Nemr R, Echtay A, Dashti EA, Almawi AW, Al-Busaidi AS, et al. (2012) Strong association of common variants in the IGF2BP2 gene with type 2 diabetes in Lebanese Arabs. Diabetes Research and Clinical Practice: 10.1016/j.diabres.2011.1012.1026.
[21]
Cauchi S, Meyre D, Durand E, Proen?a C, Marre M, et al. (2008) Post Genome-Wide Association Studies of Novel Genes Associated with Type 2 Diabetes Show Gene-Gene Interaction and High Predictive Value. PLoS ONE 3: e2031.
[22]
Horikawa Y, Miyake K, Yasuda K, Enya M, Hirota Y, et al. (2008) Replication of Genome-Wide Association Studies of Type 2 Diabetes Susceptibility in Japan. Journal of Clinical Endocrinology & Metabolism 93: 3136–3141.
[23]
Han X, Luo Y, Ren Q, Zhang X, Wang F, et al. (2010) Implication of genetic variants near SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, FTO, TCF2, KCNQ1, and WFS1 in Type 2 Diabetes in a Chinese population. BMC Medical Genetics 11: 81.
[24]
Hertel J, Johansson S, R?der H, Midthjell K, Lyssenko V, et al. (2008) Genetic analysis of recently identified type 2 diabetes loci in 1,638 unselected patients with type 2 diabetes and 1,858 control participants from a Norwegian population-based cohort (the HUNT study). Diabetologia 51: 971–977.
[25]
Lee Y-H, Kang ES, Kim SH, Han SJ, Kim CH, et al. (2008) Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population. J Hum Genet 53: 991–998.
[26]
Ng MC, Park KS, Oh B, Tam CH, Cho YM, et al. (2008) Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6,719 Asians. Diabetes 57: 2226–2233.
[27]
Wu Y, Li H, Loos RJF, Yu Z, Ye X, et al. (2008) Common Variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE Genes Are Associated With Type 2 Diabetes and Impaired Fasting Glucose in a Chinese Han Population. Diabetes 57: 2834–2842.
[28]
Hu C, Zhang R, Wang C, Wang J, Ma X, et al. (2009) PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 Are Associated with Type 2 Diabetes in a Chinese Population. PLoS ONE 4: e7643.
[29]
Tan JT, Ng DPK, Nurbaya S, Ye S, Lim XL, et al. (2010) Polymorphisms Identified through Genome-Wide Association Studies and Their Associations with Type 2 Diabetes in Chinese, Malays, and Asian-Indians in Singapore. Journal of Clinical Endocrinology & Metabolism 95: 390–397.
[30]
Rong R, Hanson RL, Ortiz D, Wiedrich C, Kobes S, et al. (2009) Association Analysis of Variation in/Near FTO, CDKAL1, SLC30A8, HHEX, EXT2, IGF2BP2, LOC387761, and CDKN2B With Type 2 Diabetes and Related Quantitative Traits in Pima Indians. Diabetes 58: 478–488.
[31]
Christiansen J, Kolte AM, Hansen TO, Nielsen FC (2009) IGF2 mRNA-binding protein 2: biological function and putative role in type 2 diabetes. J Mol Endocrinol 43: 187–195.
[32]
Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, et al. (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120: 1640–1645.
[33]
Moonesinghe R, Ioannidis JPA, Flanders WD, Yang Q, Truman BI, et al. (2012) Estimating the contribution of genetic variants to difference in incidence of disease between population groups. Eur J Hum Genet: doi: 10.1038/ejhg.2012.1015.
[34]
Grarup N, Rose CS, Andersson EA, Andersen G, Nielsen AL, et al. (2007) Studies of Association of Variants Near the HHEX, CDKN2A/B, and IGF2BP2 Genes With Type 2 Diabetes and Impaired Insulin Release in 10,705 Danish Subjects. Diabetes 56: 3105–3111.
[35]
Grarup N, Andersen G, Krarup NT, Albrechtsen A, Schmitz O, et al. (2008) Association testing of novel type 2 diabetes risk alleles in the JAZF1, CDC123/CAMK1D, TSPAN8, THADA, ADAMTS9, and NOTCH2 loci with insulin release, insulin sensitivity, and obesity in a population-based sample of 4,516 glucose-tolerant middle-aged Danes. Diabetes 57: 2534–2540.