IGF2BP2 Alternative Variants Associated with Glutamic Acid Decarboxylase Antibodies Negative Diabetes in Malaysian Subjects

Abstract

BackgroundThe 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 FindingsIGF2BP2; 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/SignificanceIGF2BP2 alternative variants were associated with GADA negative diabetes. The IGF2BP2 haplotypes and diplotypes increased the risk of diabetes in Malaysian subject.

Linking Alzheimer's disease and type 2 diabetes: Novel shared susceptibility genes detected by cFDR approach

“…15 of these SNPs reached a genome wide significance level of <5 × 10 −8 in the original meta-analysis [24]. Based on the published literature and our results, 26 SNPs and corresponding genes are associated with T2D and have been previously reported, including those in PROX1 (rs340835) [37], IGF2BP2 (rs7651090) [38], WFS1 (rs734312) [39], CDKAL1 (rs10946403/rs7741604/rs10484634/rs1012635) [28,40–42], JAZF1 (rs849135) [43], KLF14 (rs4731702/rs13234407) [44,45], TP53INP1 (rs896854) [46], SLC30A8 (rs11558471) [47], HHEX (rs7911264) [48], ZMIZ1 (rs810517) [49], IDE/KIF11 (rs6583826) [50], TCF7L2 (rs4074720/rs7079711/rs290483/rs11196212) [51–54], HMGA2 (rs2261181) [55], CHR12 (rs7132840) [56], FTO (rs9940128/rs9930506/rs8057044) [51,57], HNF1B (rs4430796) [58], BCAR1 (rs9927309) [59]. Furthermore, 40 SNPs were identified as novel variants for T2D and annotated at 44 different genes, of which 23 genes have been reported to be significantly related with T2D in earlier researches [15,43,60–67], and remaining 21 genes were not previously detected in earlier T2D GWAS studies.…”

A Simplified Screening Model to Predict the Risk of Gestational Diabetes Mellitus in Caucasian and Latin American Pregnant Women

“…rs1387153 is also related with an increase in FPG levels and T2DM prevalence in European populations [35]. The IGF2BP2 variant rs7651090 is described in Malaysian subjects with glutamic acid decarboxylase antibody (GADA)negative diabetes [36]. rs1371614 DPYSL5 and rs9368222 CDKAL1 variants were previously reported in GDM women in our cohort [22].…”

The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers

“…IGF2BP2 rs11705701 has been associated with low body fat, which contributes to insulin resistance and consequently T2D risk in Mexican American population [53]. IGF2BP2 rs11705701 has also been associated with Japanese population \ [32] Asians \ [27,33] Iceland's population Decreased fasting insulin levels, impaired β-cell function [34] Greek-Cypriot population \ [35] Czech population \ [26] Germany population \ [33,36] Lebanese Arabs \ [37] Arab population \ [38] Moroccan population \ [38] Tunisian population \ [39] India's population \ [40] \ Predict the occurrence and diagnosis of GDM [43] Poland population Influenced the length of gestation and the Apgar scores of newborns [44] rs1470579 Chinese Han population Reduced the therapeutic efficacy of repaglinide and the effect of pioglitazone on PPG, TG, and HDL-C [29,30,42] Lebanese population \ [46] Iranian population \ [47] rs11705701 Mexican American population Affected insulin resistance [53] Russian population Contributed to T2D risk, decreased levels of p58 and increased levels of p66 of the IGF2BP2 in adipose tissue of non-obese individuals [51] Poland population Influenced the length of gestation and the Apgar scores of newborns [44] \ Associated with prediabetes [54] rs9826022 \ \ [48] rs11927381 Chinese Han population \ [55] rs7640539 [55] rs6777038 \ Associated with GADA negative diabetes [56] rs16860234 rs7651090…”

“…Besides, IGF2BP2 rs11927381 and rs7640539 are all associated with the risk of developing T2D among Chinese Han population [55]. Meanwhile, rs6777038, rs16860234 and rs7651090 of IGF2BP2 are closely linked with glutamic acid decarboxylase (GAD) antibody-negative diabetes [56].…”