Involvement of miR‐126 rs4636297 and miR‐146a rs2910164 polymorphisms in the susceptibility for diabetic retinopathy: a case–control study in a type 1 diabetes population
Abstract:Background and purpose
MicroRNAs (miRNAs) are small non‐coding RNAs that regulate gene expression. MiRNA‐126 and miRNA‐146a have been described as having abnormal expressions in diabetic retinopathy (DR) patients. Polymorphisms in genes codifying miRNAs (miRSNPs) may alter the expression of the corresponding miRNA and, thus, interfere with susceptibility to DR. Therefore, miRSNPs in miR‐126 and miR‐146a genes could be associated with DR susceptibility. The purpose of this study was to investigate the associati… Show more
“…Results indicated there was a significant difference in the genotype distribution between patients with aged over 20 and patients aged less than 40 years old (Table 11). Results indicated that there was a significant differences in the rs3730089 SNP genotype (GG, GA, AA) between cases (09, 49, 42) and controls (18,69,35) with a p-value = 0.03 (Table 12). The A allele was associated with T2D with OR (95% CI) = 1.49 (1.01-2.21), RR = 1.19 (1.01-1.41), p-value = 0.04 (Table 13).…”
Section: Resultsmentioning
confidence: 99%
“…Furthermore, reduced plasma miR-126 has been suggested as a biomarker for T2DM [ 17 ]. In addition, the miR-126 rs4636297 SNP was associated with DR in T1DM patients from Brazil [ 18 ]. PI3K is a heterodimeric enzyme composed of a catalytic subunit (p110) and a regulatory subunit (p85) [ 19 ].…”
Type 2 diabetes is a metabolic disease characterized by elevated blood sugar. It has serious complications and socioeconomic impact. The MicroRNAs are short single-stranded and non-coding RNA molecules. They regulate gene expression at the post-transcriptional levels. They are important for many physiological processes including metabolism, growth, and others. The phosphoinositide 3-kinase (PI3K) is important for insulin signaling and glucose uptake. The genome wide association studies have identified the association of certain loci with diseases including T2D. In this study we have examined the association of miR126 rs4636297 and Phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) gene Variations rs7713645, rs706713 (Tyr73Tyr), and rs3730089 (Met326Ile) with T2D using the amplification refractory mutation system PCR. Results indicated that there was a significant different (p-value < 0.05) in the Mir126 rs4636297 genotypes distribution between cases and controls, and the minor allele of the rs4636297 was also associated with T2D with OR = 0.58, p-value < 0.05. In addition results showed that there were significant differences (p-value < 0.05) of rs4636297 genotype distribution of patients with normal and patient with abnormal lipid profile. Results also showed that the PIK3R1 rs7713645 and rs3730089 genotype distribution was significantly different between cases and controls with a p-values < 0.05. In addition, the minor allele of the rs7713645 and rs3730089 were associated with T2D with OR = 0.58, p-value < 0.05). We conclude that the Mir126 rs4636297 and PIK3R1 SNPs (rs7713645 and rs3730089) were associated with T2D. These results need verification in future studies with larger sample sizes and in different populations. Protein-protein interaction and enzyme assay studies are also required to uncover the effect of the SNPs on the PI3K regulatory subunit (PI3KR1) and PI3K catalytic activity.
“…Results indicated there was a significant difference in the genotype distribution between patients with aged over 20 and patients aged less than 40 years old (Table 11). Results indicated that there was a significant differences in the rs3730089 SNP genotype (GG, GA, AA) between cases (09, 49, 42) and controls (18,69,35) with a p-value = 0.03 (Table 12). The A allele was associated with T2D with OR (95% CI) = 1.49 (1.01-2.21), RR = 1.19 (1.01-1.41), p-value = 0.04 (Table 13).…”
Section: Resultsmentioning
confidence: 99%
“…Furthermore, reduced plasma miR-126 has been suggested as a biomarker for T2DM [ 17 ]. In addition, the miR-126 rs4636297 SNP was associated with DR in T1DM patients from Brazil [ 18 ]. PI3K is a heterodimeric enzyme composed of a catalytic subunit (p110) and a regulatory subunit (p85) [ 19 ].…”
Type 2 diabetes is a metabolic disease characterized by elevated blood sugar. It has serious complications and socioeconomic impact. The MicroRNAs are short single-stranded and non-coding RNA molecules. They regulate gene expression at the post-transcriptional levels. They are important for many physiological processes including metabolism, growth, and others. The phosphoinositide 3-kinase (PI3K) is important for insulin signaling and glucose uptake. The genome wide association studies have identified the association of certain loci with diseases including T2D. In this study we have examined the association of miR126 rs4636297 and Phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) gene Variations rs7713645, rs706713 (Tyr73Tyr), and rs3730089 (Met326Ile) with T2D using the amplification refractory mutation system PCR. Results indicated that there was a significant different (p-value < 0.05) in the Mir126 rs4636297 genotypes distribution between cases and controls, and the minor allele of the rs4636297 was also associated with T2D with OR = 0.58, p-value < 0.05. In addition results showed that there were significant differences (p-value < 0.05) of rs4636297 genotype distribution of patients with normal and patient with abnormal lipid profile. Results also showed that the PIK3R1 rs7713645 and rs3730089 genotype distribution was significantly different between cases and controls with a p-values < 0.05. In addition, the minor allele of the rs7713645 and rs3730089 were associated with T2D with OR = 0.58, p-value < 0.05). We conclude that the Mir126 rs4636297 and PIK3R1 SNPs (rs7713645 and rs3730089) were associated with T2D. These results need verification in future studies with larger sample sizes and in different populations. Protein-protein interaction and enzyme assay studies are also required to uncover the effect of the SNPs on the PI3K regulatory subunit (PI3KR1) and PI3K catalytic activity.
“…Single nucleotide polymorphisms in miRNAs were associated with late complications. An rs2910164 polymorphism in seed sequence within miR-146a, leading to a reduction in mature miR-146a, was associated with diabetic nephropathy, and retinopathy [89,96]. In the southern Brazilian population, an association between the A allele of miR-126 rs4636297 and protection against diabetic retinopathy was observed [96].…”
Section: Mirnas and Late Complicationsmentioning
confidence: 99%
“…An rs2910164 polymorphism in seed sequence within miR-146a, leading to a reduction in mature miR-146a, was associated with diabetic nephropathy, and retinopathy [89,96]. In the southern Brazilian population, an association between the A allele of miR-126 rs4636297 and protection against diabetic retinopathy was observed [96]. miR-449b rs10061133 polymorphism was significantly associated with a decrease in risk for proliferative diabetic retinopathy, with a minor G allele being protective against diabetic retinopathy by altering a Dicer cleavage site [97].…”
Type 1 diabetes is a chronic autoimmune disease in which the destruction of pancreatic β cells leads to hyperglycemia. The prevention of hyperglycemia is very important to avoid or at least postpone the development of micro- and macrovascular complications, also known as late complications. These include diabetic retinopathy, chronic renal failure, diabetic neuropathy, and cardiovascular diseases. The impact of long-term hyperglycemia has been shown to persist long after the normalization of blood glucose levels, a phenomenon known as metabolic memory. It is believed that epigenetic mechanisms such as DNA methylation, histone modifications, and microRNAs, play an important role in metabolic memory. The aim of this review is to address the impact of long-term hyperglycemia on epigenetic marks in late complications of type 1 diabetes.
“…The rs4636297 (A>G) SNP is situated in the flanking region of the MIR126 gene within an intronic part of the epidermal growth factor-like protein 7 (EGFL7) gene and has been connected to post-transcriptional alterations in circulating miR-126 levels [ 28 ]. The miR-126 is an endothelial-specific miRNA and is reported as linked to endothelial activation and damage [ 29 ].…”
The most serious type of coronary artery disease (CAD), acute myocardial infarction (AMI), is a major global cause of death. The development of AMI is accompanied by several risk factors. AMI may be caused by variations in the microRNA (miRNA) genes, which have a negative impact on miRNA-mediated regulation of gene expression. The target mRNAs are dysregulated because of these genetic changes in the miRNA genes, which interfere with the vital biological processes that result in AMI. Using allele-specific PCR, the aim of the study is to examine the association of the variants (rs2910164, rs4636297, and rs895819) in MIR146A, MIR126, and MIR27A with AMI susceptibility. A difference in genotype distribution among the patients and control for variation rs2910164 was identified by co-dominant [χ2 = 68.34,2; P value<0.0001], dominant (G/G vs G/C + C/C) [OR = 4.167 (2.860–6.049); P value<0.0001], recessive (C/C vs G/C + G/G) [OR = 0.2584 (0.1798–0.3731); P value<0.0001], and additive models [OR = 3.847 (2.985–4.959); P value<0.0001]. Whereas the association of rs4636297 was investigated by co-dominant [χ2 = 6.882,2; P value = 0.0320], dominant (G/G vs G/A + A/A) [OR = 0.6914 (0.4849–0.9948); P value = 0.0489], recessive (A/A vs A/G + G/G) [OR = 2.434 (0.9849–5.616830); P value = 0.0595], and additive models [OR = 0.7716 (0.6000–0.9918); P value = 0.0433]. Similarly, association of rs895819 was determined by co-dominant [χ2 = 5.277, 2; P value = 0.0715], dominant (G/G vs G/A + A/A) [OR = 1.654(0.9819–2.801); P value = 0.06440], recessive (A/A vs A/G + G/G) [OR = 0.7227 (0.5132–1.022); P value = 0.0748], and additive models [OR = 1.3337 (1.041–1.719); P value = 0.0233]. The results of this study found a significant association of rs2910164 and rs4636297 with AMI and are considered as the risk factor for AMI in the Pakistani population. We observed no significant association of the variant MIR27A (rs895819) with AMI incidence.
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