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.
Highlights
Type 2 diabetes (T2D) mellitus is a heterogeneous complex disease in which both predisposing genetic factors and precipitating environmental factors contribute to the development of the disease [1,2]
Among the excluded articles were those in which any one of the following reasons applied: (a) the paper was a review article; (b) the article was duplicative of another publication from the same population; (c) the article was a survey study; (d) insufficient data were provided to determine an estimate of OR and a 95% confidence intervals (CIs)
The largest control group consisted of 2,544 interviewed healthy individuals with neither a personal nor a family history of T2D or related diseases; the smaller control group based on a self-reported medical questionnaire, included 784 healthy individuals screened only for the absence of T2D, without a personal interview
Summary
Type 2 diabetes (T2D) mellitus is a heterogeneous complex disease in which both predisposing genetic factors and precipitating environmental factors contribute to the development of the disease [1,2]. HMGA1 Gene Variant and Type 2 Diabetes Risk mortality, and its effect on health care costs, many studies have been performed in recent years to elucidate the pathogenetic mechanisms of this disease [3]. Despite the efforts and the recent genomewide association studies (GWAS), these genetic variants explain only a small proportion of heritability of T2D [6,7], a phenomenon referred to as the “missing heritability” problem [8], which may result from the involvement of rare variants not included in the GWAS database, or variants having a minor allele frequency below the minimum threshold value (5–10%) of GWAS, or from the action of multiple genes that interact with each other in an epistatic manner [5,6]
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