Influence of IGF2BP2, HMG20A, and HNF1B genetic polymorphisms on the susceptibility to Type 2 diabetes mellitus in Chinese Han population

Abstract

Background: The present study aimed to investigate the roles of insulin related gene IGF2BP2, HMG20A, and HNF1B variants in the susceptibility of Type 2 diabetes mellitus (T2DM), and to identify their association with age, gender, BMI, and smoking and alcohol drinking behavior among the Han Chinese population. Methods: About 508 patients with T2DM and 503 healthy controls were enrolled. Rs11927381 and rs7640539 in IGF2BP2, rs7178572 in HMG20A, rs4430796, and rs11651052 in HNF1B were genotyped by using the Agena MassARRAY. Odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistic regression. Results: We found that HMG20A rs7178572 (OR = 1.25, P = 0.015) and HNF1B rs11651052 (OR = 1.26, P = 0.019) increased the risk of T2DM. Rs7178572, rs4430796, and rs11651052 might be related to the higher T2DM susceptibility not only by itself but also by interacting with age, gender smoking, and alcohol drinking. Rs11927381 also conferred the higher T2DM susceptibility at age ≤ 59 years. Besides, rs7178572-AA (P = 0.032) genotype and rs11651052 GG (P = 0.018) genotype were related to higher glycated hemoglobin and insulin level, respectively. Conclusion: Specifically, we first found that rs11927381, rs7640539, and rs11651052 were associated with risk of T2DM among the Han Chinese population. We also provide evidence that age, gender, BMI, smoking, and drinking status have an interactive effect with these variants on T2DM susceptibility.

The metabesity factor HMG20A potentiates astrocyte survival and reactive astrogliosis preserving neuronal integrity

“…Of particular interest is the chromatin remodeling factor HMG20A that we recently reported to be essential for pancreatic islet beta-cell functional maturation and adaptation to stress conditions such as hyperglycemia and pregnancy 17 , 18 . Consistent with these functional data small nucleotide polymorphisms (SNPs) in the HMG20A gene have been associated to T2DM as well as gestational diabetes mellitus (GDM) in Asian/Indian and European populations 19 - 25 . HMG20A is also a key regulator of neuronal differentiation 26 by exerting global genomic changes through establishing active or silent chromatin 27 .…”

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…”

“…On the other hand, rs9826022, a rare mutation in the 3′downstream region of IGF2BP2, is closely associated with T2D [47]. 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].…”

The putative causal effect of type 2 diabetes in risk of cataract: a Mendelian randomization study in East Asian

“…Therefore, we collected information from a total of 254 SNPs in ClinVar 39 and genes in Malacards (supported by trustworthy sources or Cochrane based reviews 40 ) for further analyses (Table S5). We identified gene HNF1B (hepatocyte nuclear factor 1 β ; Chromosome: 17: 36,046,434–36,105,096) and two SNPs (i.e., rs121918673 [Chromosome: 17: 36,061,127] and rs1555818071 [Chromosome: 17: 36,047,338]; located within gene HNF1B ) that located within the significant genomic region on chromosome 17: 34,395,061–36,495,389 and reported to be associated with type 2 diabetes 41, 42 . In contrast, no SNPs or genes located in the ρ-HESS estimated significant genomic regions were found to be associated with cataract risk.…”

“…Therefore, we collected information from a total of 254 SNPs in ClinVar 39 and genes in Malacards (supported by trustworthy sources or Cochrane based reviews 40 ) for further analyses (Table S5). We identified gene HNF1B (hepatocyte 41,42 . In contrast, no SNPs or genes located in the ρ -HESS estimated significant genomic regions were found to be associated with cataract risk.…”