The Association between HMGA1 rs146052672 Variant and Type 2 Diabetes: A Transethnic Meta-Analysis

Abstract

The high-mobility group A1 (HMGA1) gene has been previously identified as a potential novel candidate gene for susceptibility to insulin resistance and type 2 diabetes (T2D) mellitus. For this reason, several studies have been conducted in recent years examining the association of the HMGA1 gene variant rs146052672 (also designated IVS5-13insC) with T2D. Because of non-univocal data and non-overlapping results among laboratories, we conducted the current meta-analysis with the aim to yield a more precise and reliable conclusion for this association. Using predetermined inclusion criteria, MEDLINE, PubMed, Web of Science, Scopus, Google Scholar and Embase were searched for all relevant available literature published until November 2014. Two of the authors independently evaluated the quality of the included studies and extracted the data. Values from the single studies were combined to determine the meta-analysis pooled estimates. Heterogeneity and publication bias were also examined. Among the articles reviewed, five studies (for a total of 13,789 cases and 13,460 controls) met the predetermined criteria for inclusion in this meta-analysis. The combined adjusted odds ratio estimates revealed that the rs146052672 variant genotype had an overall statistically significant effect on increasing the risk of development of T2D. As most of the study subjects were Caucasian, further studies are needed to establish whether the association of this variant with an increased risk of T2D is generalizable to other populations. Also, in the light of this result, it would appear to be highly desirable that further in-depth investigations should be undertaken to elucidate the biological significance of the HMGA1 rs146052672 variant.

Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations

“…Key roles of Notch signaling also include regulation of adipocyte homeostasis and skeletal muscle homeostasis ( Bi & Kuang, 2015 ). One upstream regulator of JAG1, HMGA1 is also involved in the molecular mechanism of T2D ( Bianco et al, 2015 ). It has been reported that the expression of JAG1 is down-regulated upon HMGA1 depletion by siRNA ( Pegoraro et al, 2013 ).…”

Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links

“…Many studies from our group have demonstrated the role of HMGA1 in the transcriptional control of glucose metabolism, being a key regulator of the insulin receptor ( INSR ), insulin-like growth factor binding protein 1 ( IGFBP1 ), retinol binding-protein 4 ( RBP4 ), visfatin , and insulin ( INS ) genes ( 88 – 93 ), as well as an important mediator of insulin action ( 94 ). Defects in HMGA1 protein, or the association with functional HMGA1 variants, among which the most common rs139876191 variant (previously named rs146052672), cause a decrease in INSR expression and a trans-ethnic increased susceptibility to either type 2 DM ( 26 , 95 – 98 ) or metabolic syndrome ( 99 ). Besides its effects on glucose homeostasis, HMGA1 plays a role in adipogenesis and lipid metabolism ( 100 – 102 ), while the HMGA1 rs139876191 variant correlates with body mass index, and reduced HDL levels in patients with metabolic syndrome and type 2 DM ( 97 , 99 ).…”

Association ofIL-16gene polymorphisms with the risk of developing type 2 diabetes mellitus in the Chinese Han population

“…In China, the onset age of T2DM shows a younger trend, and the morbidity has been ranked first in the world [3,4]. Substantial evidence demonstrate that T2DM can be attributed by lifestyle, environmental and genetic factors [5][6][7][8]. Although the etiology of T2DM is complex and needs further study, genetic factors have been identified to be an important cause, and an increasing number of candidate genes have been identified recent years [9,10].…”