Polymorphism of HMGA1 is associated with increased risk of type 2 diabetes among Chinese individuals

Abstract

HMGA1 is an important susceptibility locus that confers a high cross-race risk of the development of type 2 diabetes.

Recent advances in the molecular genetics of type 2 diabetes mellitus

“…Once again, in transformed lymphoblasts from the patients with the HMGA1 rs146052672 variant, restoration of HMGA1 protein expression by complementary DNA transfection (in the sense but not antisense direction) restored INSR protein expression and insulin binding to these cells [40] . Although not replicated in a heterogeneous French population [73] , the HMGA1 rs146052672 variant was significantly associated with T2DM among Chinese [41] and Hispanic-American [38] individuals. Further evidence, implicating the HMGA1 locus as one conferring a high cross-race risk for the development of insulin resistant diseases, has been provided recently by showing that the HMGA1 rs146052672 variant significantly associates with the metabolic syndrome in Italian and Turkish individuals and predisposes these (and other) populations to the unfavorable anthropometric and metabolic traits of the metabolic syndrome [74,42] .…”

Deriving at candidate genes of metabolic stress from pancreas of WNIN/GR-Ob mutant rats

“…28 An upregulation in the expression of CCAAT/enhancer binding proteins (CEBPA,CEBPE) by a fold of 2.73, 2.41 fold, have been linked to obesity in humans 29 and HMGA1 upregulated by 1.66 fold, is a key regulator of Insulin receptor gene expression, has been well associated with T2D in Chinese individuals. 30 At the biochemical level, defects in key enzymes of glycolysis 31 and gluconeogenesis 31 have been reported to contribute toward impaired β-cell functions. Decreased expression of Glucokinase (-1.93 fold) is also associated with hyperglycemia and IGT.…”

Association of ICAM-1 and HMGA1 Gene Variants with Retinopathy in Type 2 Diabetes Mellitus Among Chinese Individuals

“…11,21 Nevertheless, there are not any existing literature on similar issue in other Chinese groups. In this study, we investigated the possible genetic variant association of these two insulin resistance-related genes, ICAM-1 and HMGA1, with the susceptibility of DR in a Chinese T2DM cohort; however, no association was documented herein.…”

“…19,20 It has recently been suggested that the IVS5-13insC variant in HMGA1 gene may strongly contribute to the correlation of insulin resistance and T2DM risk. [21][22][23] The interaction of insulin with target cells is mediated by the INSR, a glycoprotein that is located on the plasma membrane and serves a crucial role both in directing insulin to target tissues and in initiating the responses of these tissues to the hormone. 22,23 Recently, Chiefari and colleagues24,25 demonstrated that individuals with T2DM had an increased prevalence over controls of the heterozygous variant IVS5-13insC of the HMGA1 gene, and HMGA1 is a novel downstream nuclear target of the insulin receptor signaling pathway.…”

“…22,23 Recently, Chiefari and colleagues24,25 demonstrated that individuals with T2DM had an increased prevalence over controls of the heterozygous variant IVS5-13insC of the HMGA1 gene, and HMGA1 is a novel downstream nuclear target of the insulin receptor signaling pathway. Liu et al 21 discovered that the IVS5-13insC variant of HMGA1 gene increased the risk of T2DM among Chinese individuals. However, Marquez 26 pointed out that HMGA1 variant is not associated with T2DM risk.…”