English
Abstract
MicroRNAs (miRNAs), small non-coding RNAs, have emerged as promising diagnostic and prognostic biomarkers for various diseases. However, their role in the pathogenesis of type 2 diabetes mellitus (T2DM) remains insufficiently defined. This case–control study investigated associations between genetic variants in miRNA genes and susceptibility to T2DM in a Greek population. A total of 716 individuals with T2DM and 569 controls (HbA1c < 6.5% and fasting plasma glucose < 126 mg/dL) were included. Genomic DNA was extracted from whole blood and genotyped using the Illumina Infinium PsychArray platform. Polymorphisms in MIR124a, MIR27a, MIR146a, MIR34a, MIRLET7A2, MIR128a, MIR196a2, MIR499a, MIR4513, and MIR149 were analyzed, with all SNPs within 20 kb upstream and downstream of each gene assessed. Allele frequencies were compared between cases and controls using PLINK. Significant associations with increased T2DM risk were observed for rs1531212 (OR = 1.375, p = 0.018) in MIR23aHG (containing MIR27a) and rs6120777 (OR = 1.27, p = 0.018) in MYH7B, upstream of MIR499a. Conversely, rs2425012 (OR = 0.794, p = 0.018) upstream of MIR27a, as well as rs883517 (OR = 0.728, p = 0.024) and rs2961920 (OR = 0.80, p = 0.041) upstream of MIR146a, appeared protective. Under the dominant model, two additional associations emerged: rs3746435 (OR = 1.239, p = 0.025) in MYH7B (upstream of MIR499a) and rs3746444 (OR = 1.235, p = 0.046) in MIR499a. In conclusion, this study identifies three novel genetic variants near MIR27a and MIR499a that may influence susceptibility to T2DM. These findings warrant validation in larger cohorts and functional studies to clarify their role in T2DM pathogenesis.
Keywords:
type 2 diabetes; SNPs; miRNAs; genetic predisposition
1. Introduction
Diabetes mellitus (DM) is a chronic disorder of glucose metabolism associated with impaired quality of life, severe complications, and a substantial burden on health care systems, and it has reached epidemic proportions worldwide. While type 1 diabetes mellitus (T1DM) typically manifests early in life, the incidence of type 2 diabetes mellitus (T2DM) increases progressively with age. According to the International Diabetes Federation, the global prevalence of DM is projected to reach 700 million by 2045. Diagnosis is based on plasma glucose or glycated hemoglobin (HbA1c) thresholds, established primarily through large-scale studies—mostly in T1DM cohorts—that evaluated the relationship between glycemic measures and diabetic complications, particularly microvascular organ damage [1]. Given the complex etiology of DM, genetic factors are recognized as important contributors to both hyperglycemia and its complications. Nevertheless, the precise genetic architecture of T2DM remains incompletely understood.
Recent advances in techniques such as genome-wide association studies (GWAS) have enabled the identification of numerous single-nucleotide polymorphisms (SNPs) and genomic loci associated with diabetes mellitus (DM) and related cardiometabolic traits [2]. A key limitation of genetic studies in this field is the lack of standardized criteria for defining cases and controls. In many GWAS, DM is classified using vague criteria, including self-reported diagnosis or the use of antidiabetic therapy, rather than uniform, clinically validated definitions.
MicroRNAs (miRNAs) are small non-coding RNAs, 19–24 nucleotides in length, that regulate gene expression by repressing translation or, to a lesser extent, by reducing mRNA stability through interactions with complementary sequences in the 3′ untranslated region (3′UTR) of target genes. The seed sequence, defined as nucleotides 2–8 of miRNA, plays a critical role in target recognition and regulation. Genetic variation within either the miRNA seed region or the complementary 3′UTR sequence of a target gene can impair binding specificity, leading to aberrant gene expression [3,4,5]. Both computational and experimental studies have demonstrated that variants in miRNA-binding sites may alter disease susceptibility by disrupting canonical recognition sites or creating novel binding sites [6,7,8]. Several studies have investigated the role of miRNAs in diabetes mellitus (DM) and obesity [9,10]. Although these studies have identified diverse variants affecting protein function and regulatory mechanisms, the application of miRNAs for target prediction or diagnosis remains limited by poor accuracy and high false-positive rates [11,12,13]. Furthermore, investigations of genomic variations in miRNA-binding sites are still relatively scarce. The aim of the present study was to investigate, for the first time in a Greek population, the association between genomic variations in miRNA seed sequences, their complementary sequences, or binding sites, and the risk of developing T2DM in elderly individuals (>65 years).
Source: MDPI
Original link:https://www.mdpi.com/1422-0067/26/21/10447
The FAI climbed 5.9 percent year-on-year in the first 11 months of 2018, quickening from the 5.7-percent growth in Jan-Oct, the National Bureau of Statistics (NBS) said Friday in an online statement.
The key indicator of investment, dubbed a major growth driver, hit the bottom in August and has since started to rebound steadily.
In the face of emerging economic challenges home and abroad, China has stepped up efforts to stabilize investment, in particular rolling out measures to motivate private investors and channel funds into infrastructure.
Friday's data showed private investment, accounting for more than 60 percent of the total FAI, expanded by a brisk 8.7 percent.
NBS spokesperson Mao Shengyong said funds into weak economic links registered rapid increases as investment in environmental protection and agriculture jumped 42 percent and 12.5 percent respectively, much faster than the average.
In breakdown, investment in high-tech and equipment manufacturing remained vigorous with 16.1-percent and 11.6-percent increases respectively in the first 11 months. Infrastructure investment gained 3.7 percent, staying flat. Investment in property development rose 9.7 percent, also unchanged.