Abstract:Type 2 diabetes mellitus (T2DM) belongs to the diseases with hereditary predisposition, so both environmental and genetic factors contribute to its development. Recent studies have demonstrated that the skeleton realizes systemic regulation of energy metabolism through the secretion of osteocalcin (OCN). Thus, the association analysis between HindIII single nucleotide polymorphism of OCN gene (BGLAP) promoter region and T2DM development in Ukrainian population was carried out. 153 individuals diagnosed with T2… Show more
“…In this study, we continued to study the association between BGLAP rs1800247 SNP and T2DM development among Ukrainians. The lack of studied correlation matches both our previous research [9] and Das et al study, which excluded BGLAP rs1800247 SNP as a T2DM potential risk factor [13].…”
Section: Discussionsupporting
confidence: 89%
“…Polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) was used for BGLAP rs1800247-genotyping. Full information about genotyping protocol was presented in our previous research [9].…”
The risk T2DM development depends on hereditary predisposition. According to the current data, skeleton enhances insulin gene expression in pancreatic β-cells as well as increases insulin sensitivity of adipocytes, myocytes and hepatocytes through the secretion of unOCN.The aim. To analyze the link between rs1800247 SNP and T2DM occurrence depending on the AH presence, as well as association between rs1800247 and systolic, diastolic, pulse, mean blood pressure among patients with diabetes.Materials and Methods. This study included 153 patients with diagnosed T2DM and 311 individuals without any carbohydrate metabolism disorders. Polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) was used for BGLAP rs1800247-genotyping. Logistic regression with interaction term “genotype × AH” was used to estimate the association between BGLAP rs1800247-genotypes and T2DM development under dominant, recessive, over-dominant and additive models of inheritance. Linear regression was performed to investigate the influence of minor C-allele on the arterial blood pressure. All calculations were performed using Statistical Package for the Social Sciences software (SPSS, version 22.0, Chicago, IL, USA). A value of P ˂ 0,05 was considered as significant.Results. No association was found between rs1800247 single nucleotide polymorphism and T2DM development neither in AH patients, nor in subjects without AH (Paint b > 0,05). There was no impact of rs1800247 genotypes on systolic, diastolic, pulse and mean blood pressure among patients with T2DM (P > 0,05).Conclusion. It was found the lack of association between rs1800247 SNP and T2DM development as well as blood pressure parameters. Further studies with extended groups of comparison are needed for the confirmation of results. This research was a part of the scientific project “Molecular-genetic and morphological features of lower limb tissues regeneration under conditions of chronic hyperglycemia” (0117U003926).
“…In this study, we continued to study the association between BGLAP rs1800247 SNP and T2DM development among Ukrainians. The lack of studied correlation matches both our previous research [9] and Das et al study, which excluded BGLAP rs1800247 SNP as a T2DM potential risk factor [13].…”
Section: Discussionsupporting
confidence: 89%
“…Polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) was used for BGLAP rs1800247-genotyping. Full information about genotyping protocol was presented in our previous research [9].…”
The risk T2DM development depends on hereditary predisposition. According to the current data, skeleton enhances insulin gene expression in pancreatic β-cells as well as increases insulin sensitivity of adipocytes, myocytes and hepatocytes through the secretion of unOCN.The aim. To analyze the link between rs1800247 SNP and T2DM occurrence depending on the AH presence, as well as association between rs1800247 and systolic, diastolic, pulse, mean blood pressure among patients with diabetes.Materials and Methods. This study included 153 patients with diagnosed T2DM and 311 individuals without any carbohydrate metabolism disorders. Polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) was used for BGLAP rs1800247-genotyping. Logistic regression with interaction term “genotype × AH” was used to estimate the association between BGLAP rs1800247-genotypes and T2DM development under dominant, recessive, over-dominant and additive models of inheritance. Linear regression was performed to investigate the influence of minor C-allele on the arterial blood pressure. All calculations were performed using Statistical Package for the Social Sciences software (SPSS, version 22.0, Chicago, IL, USA). A value of P ˂ 0,05 was considered as significant.Results. No association was found between rs1800247 single nucleotide polymorphism and T2DM development neither in AH patients, nor in subjects without AH (Paint b > 0,05). There was no impact of rs1800247 genotypes on systolic, diastolic, pulse and mean blood pressure among patients with T2DM (P > 0,05).Conclusion. It was found the lack of association between rs1800247 SNP and T2DM development as well as blood pressure parameters. Further studies with extended groups of comparison are needed for the confirmation of results. This research was a part of the scientific project “Molecular-genetic and morphological features of lower limb tissues regeneration under conditions of chronic hyperglycemia” (0117U003926).
“…3 , and the detailed information of KEGG pathway and GO terms is listed in Table 3 and Additional file 3 , respectively. The enriched pathways (eg, starch and sucrose metabolism and MAPK signaling pathway) and related genes (eg, IL1B and ENPP1 ) have been reported association with T2DM [ 22 – 24 ], which indicated that lnc-HIST1H2AG-6 and lnc-AIM1-3 might play a role in T2DM. Fig.…”
Background
Type 2 diabetes mellitus (T2DM) is mainly affected by genetic and environmental factors; however, the correlation of long noncoding RNAs (lncRNAs) with T2DM remains largely unknown.
Methods
Microarray analysis was performed to identify the differentially expressed lncRNAs and messenger RNAs (mRNAs) in patients with T2DM and healthy controls, and the expression of two candidate lncRNAs (lnc-HIST1H2AG-6 and lnc-AIM1-3) were further validated using quantitative real-time polymerase chain reaction (qRT-PCR). Spearman’s rank correlation coefficient was used to measure the degree of association between the two candidate lncRNAs and differentially expressed mRNAs. Furthermore, the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway and GO (Gene Ontology) enrichment analysis were used to reveal the biological functions of the two candidate lncRNAs. Additionally, multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed.
Results
The microarray analysis revealed that there were 55 lncRNAs and 36 mRNAs differentially expressed in patients with T2DM compared with healthy controls. Notably, lnc-HIST1H2AG-6 was significantly upregulated and lnc-AIM1-3 was significantly downregulated in patients with T2DM, which was validated in a large-scale qRT-PCR examination (90 controls and 100 patients with T2DM). Spearman’s rank correlation coefficient revealed that both lncRNAs were correlated with 36 differentially expressed mRNAs. Furthermore, functional enrichment (KEGG and GO) analysis demonstrated that the two lncRNA-related mRNAs might be involved in multiple biological functions, including cell programmed death, negative regulation of insulin receptor signal, and starch and sucrose metabolism. Multivariate logistic regression analysis revealed that lnc-HIST1H2AG-6 and lnc-AIM1-3 were significantly correlated with T2DM (OR = 5.791 and 0.071, respectively, both P = 0.000). Furthermore, the ROC curve showed that the expression of lnc-HIST1H2AG-6 and lnc-AIM1-3 might be used to differentiate patients with T2DM from healthy controls (area under the ROC curve = 0.664 and 0.769, respectively).
Conclusion
The profiles of lncRNA and mRNA were significantly changed in patients with T2DM. The expression levels of lnc-HIST1H2AG-6 and lnc-AIM1-3 genes were significantly correlated with some features of T2DM, which may be used to distinguish patients with T2DM from healthy controls and may serve as potential novel biomarkers for diagnosis in the future.
“…The content of COL1 not only reflects the mature state of osteoblasts, but also affects the strength of bone, which serves an important role in all stages of osteoblast differentiation [ 38 ]. Known as bone Y-carboxyglutamate protein, OCN is an important bone matrix protein synthesized and secreted by osteoblasts [ 39 ]. It is a specific non-collagen matrix protein and a characteristic marker protein of osteocytes.…”
Osteoporosis poses a threat to human health worldwide. To date, there have been few studies regarding targeted treatment of osteoporosis. We aimed to identify the possible molecular mechanism of circular RNA (circ)_0062582 in osteogenic differentiation, and the interactions among circ_0062582, microRNA-145 (miR-145) and core-binding factor subunit β (CBFB). The proliferation of human bone marrow mesenchymal stem cells (hBMSCs) was tested with a cell counting kit-8 assay. Circ_0062582, miR-145 and CBFB were overexpressed by transient transfection. Dual-luciferase reporter assay system was used to analyze the combination among circ_0062582, miR-145 and CBFB. Additionally, the levels of circ_0062582, miR-145, CBFB, osterix (OSX), osteocalcin (OCN) and collagen type 1 (COL1) were detected by means of RT-qPCR or western blot analysis. Alkaline phosphatase and Alizarin red stainings were performed to analyze the degree of osteogenic differentiation under the control of circ_0062582, miR-145 and CBFB. The results demonstrated that circ_0062582 level was notably elvated during osteogenic differentiation of hBMSCs. Circ_0062582 overexpression significantly promoted osteogenic differentiation and upregulated the levels of osteogenic differentiation-related proteins, including OSX, OCN and COL1. In addition, miR-145, which was identified as the target gene of circ_0062582, could specifically target CBFB 3 -UTR regions. Next, these changes caused by the overexpression of circ_0062582 were reversed following the addition of miR-145 mimic. Following overexpression of CBFB, osteogenic differentiation was increased. In summary, these results demonstrated that the role of circ_0062582 in osteoporosis is mediated through regulating the expression level of CBFB via miR-145.
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