The role of MTNR1B genetic polymorphisms in type 2 diabetes mellitus
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ABSTRACT:
SUBMITTER: Shaer N
PROVIDER: S-EPMC4075489 | biostudies-literature | 2014 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundWhether melatonin receptor 1B (MTNR1B) variants are associated with type 2 diabetes mellitus (T2DM) remains unclear. Therefore, we performed this meta-analysis to better explore correlations between MTNR1B variants and T2DM.MethodsLiterature research was performed in PubMed, Medline, and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.ResultsTotally 21 studies were enrolled to analyses. Pooled overall analyses showed that MTNR1B rs10830963 variant was significantly correlated with the susceptibility to T2DM (allele model: p = 0.02, OR = 0.97, 95% CI 0.95-1.00). Further subgroup analyses by ethnicity of participants revealed that rs10830963 variant was significantly correlated with the susceptibility to T2DM in South Asians, but not in Caucasians or East Asians. No any other positive results were found in overall and subgroup analyses.ConclusionsOur findings indicated that MTNR1B rs10830963 variant might serve as a genetic biomarker of T2DM, especially in South Asians.
| S-EPMC6503061 | biostudies-literature
Project description:Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia, dyslipidemia, stroke and several other complications. Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes (T2DM). Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases, including T2DM. Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms (SNPs). The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities. This will lead to the understanding of the role of cytokine genes in T2DM risk and development. Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s) for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications. This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease. Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM.
| S-EPMC4127584 | biostudies-literature
Project description:BACKGROUND:Gestational diabetes mellitus (GDM) is a metabolic disease in pregnancy that causes carbohydrate intolerance and hyper-glycemia. Genome-wide association studies and meta-analyses have found that the single nucleotide polymorphisms (SNPs) rs1387153 and rs10830963 of the melatonin receptor 1B ( MTNR1B) gene are associated with GDM. No studies on the MTNR1B gene effect on GDM have been performed in Saudis, other Arabs, or other Middle Eastern populations. OBJECTIVES:Investigate the association of genotype or allele frequencies of the two SNPs with GDM and with clinical parameters related to GDM. DESIGN:Case-control study. SETTINGS:Tertiary care center, Riyadh. PATIENTS AND METHODS:We recruited 400 pregnant Saudi women ages 18-45 years (200 were diagnosed with GDM, and 200 were healthy controls). Biochemical assays were performed, and rs1387153 and rs10830963 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis and real-time polymerase chain reaction with TaqMan genotyping. MAIN OUTCOME MEASURES:The association of MTNR1B gene (rs1387153 and rs10830963 polymorphisms) with GDM and with biochemical parameters related to GDM. SAMPLE SIZE:200 GDM cases and 200 non-GDM controls. RESULTS:Differences in allele frequencies for GDM vs non-GMD were statistically significant or nearly significant for both SNPs after adjustment for age and body mass index. In a logistic regression analysis, genotype TT was positively associated with post-prandial blood glucose (P=.018), but other associations were not statistically significant. CONCLUSION:The odds ratios for the associations between the rs1387153 and rs10830963 SNPs and GDM exceeded 1.5-fold, which is higher than typically reported for diseases with complex genetic background. These effect sizes for GDM suggest pregnancy-specific factors related to the MTNR1B risk genotypes. LIMITATIONS:Only two SNPs were studied. CONFLICT OF INTEREST:None.
| S-EPMC6832319 | biostudies-literature
Project description:The objective of this study was to investigate whether MTNR1B gene variants influence repaglinide response in Chinese patients with newly diagnosed type 2 diabetes mellitus (T2DM). A total of 300 patients with T2DM and 200 control subjects were enrolled to identify MTNR1B rs10830963 and rs1387153 genotypes by real-time polymerase chain reaction (PCR), with subsequent high-resolution melting (HRM) analysis. Ninety-five patients with newly diagnosed T2DM were randomly selected to undergo 8 weeks of repaglinide treatment (3 mg/day). After 8-week repaglinide monotherapy, patients with at least one G allele of MTNR1B rs10830963 showed a smaller decrease in fasting plasma glucose (FPG) (P = 0.031) and a smaller increase in homeostasis model assessment for beta cell function (HOMA-B) (P = 0.002) levels than those with the CC genotype did. The T allele carriers at rs1387153 exhibited a smaller decrease in FPG (P = 0.007) and smaller increases in postprandial serum insulin (PINS) (P = 0.016) and HOMA-B (P < 0.001) levels compared to individuals with the CC genotype. These data suggest that the MTNR1B rs10830963 and rs1387153 polymorphisms are associated with repaglinide monotherapy efficacy in Chinese patients with T2DM.
| S-EPMC6855210 | biostudies-literature
Project description: Not available
| S-EPMC4659250 | biostudies-literature
Project description:BackgroundVery recently, a novel type 2 diabetes risk gene, i.e., MTNR1B, was identified and reported to affect fasting glycemia. Using our thoroughly phenotyped cohort of subjects at an increased risk for type 2 diabetes, we assessed the association of common genetic variation within the MTNR1B locus with obesity and prediabetes traits, namely impaired insulin secretion and insulin resistance.Methodology/principal findingsWe genotyped 1,578 non-diabetic subjects, metabolically characterized by oral glucose tolerance test, for five tagging single nucleotide polymorphisms (SNPs) covering 100% of common genetic variation (minor allele frequency > 0.05) within the MTNR1B locus (rs10830962, rs4753426, rs12804291, rs10830963, rs3781638). In a subgroup (N = 513), insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp, and in a further subgroup (N = 301), glucose-stimulated insulin secretion was determined by intravenous glucose tolerance test. After appropriate adjustment for confounding variables and Bonferroni correction for multiple comparisons, none of the tagging SNPs was reliably associated with measures of adiposity. SNPs rs10830962, rs4753426, and rs10830963 were significantly associated with higher fasting plasma glucose concentrations (p < 0.0001) and reduced OGTT- and IVGTT-induced insulin release (p < or = 0.0007 and p < or = 0.01, respectively). By contrast, SNP rs3781638 displayed significant association with lower fasting plasma glucose levels and increased OGTT-induced insulin release (p<0.0001 and p < or = 0.0002, respectively). Moreover, SNP rs3781638 revealed significant association with elevated fasting- and OGTT-derived insulin sensitivity (p < or = 0.0021). None of the MTNR1B tagging SNPs altered proinsulin-to-insulin conversion.Conclusions/significanceIn conclusion, common genetic variation within MTNR1B determines glucose-stimulated insulin secretion and plasma glucose concentrations. Their impact on beta-cell function might represent the prevailing pathomechanism how MTNR1B variants increase the type 2 diabetes risk.
| S-EPMC2597741 | biostudies-literature
Project description:Diabetes mellitus (DM) is a major worldwide health problem and its prevalence has been rapidly increasing in the last century. It is caused by defects in insulin secretion or insulin action or both, leading to hyperglycemia. Of the various types of DM, type 2 occurs most frequently. Multiple genes and their interactions are involved in the insulin secretion pathway. Insulin secretion is mediated through the ATP-sensitive potassium (KATP) channel in pancreatic beta cells. This channel is a heteromeric protein, composed of four inward-rectifier potassium ion channel (Kir6.2) tetramers, which form the pore of the KATP channel, as well as sulfonylurea receptor 1 subunits surrounding the pore. Kir6.2 is encoded by the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene, a member of the potassium channel genes. Numerous studies have reported the involvement of single nucleotide polymorphisms of the KCNJ11 gene and their interactions in the susceptibility to DM. This review discusses the current evidence for the contribution of common KCNJ11 genetic variants to the development of DM. Future studies should concentrate on understanding the exact role played by these risk variants in the development of DM.
| S-EPMC4584059 | biostudies-literature
Project description:IntroductionMicroRNAs (miRNA) involved in the insulin signaling pathways deeply affect the pathogenesis of T2DM. The aim of this study was to assess the association between single nucleotide polymorphisms (SNP) of the related miRNAs (let-7f rs10877887, let-7a-1 rs13293512, miR-133a-1 rs8089787, miR-133a-2 rs13040413, and miR-27a rs895819) and susceptibility to type 2 diabetes mellitus (T2DM), and its possible mechanisms.MethodsFive SNPs in miRNAs (let-7f rs10877887, let-7a-1 rs13293512, miR-133a-1 rs8089787, miR-133a-2 rs13040413, and miR-27a rs895819) involved in the insulin signaling pathways were selected and genotyped in a case-control study that enrolled 371 T2DM patients and 381 non-diabetic controls. The individual SNP association analyses, interaction analyses of SNP-SNP, SNP-environmental factors were performed. The effect the risk-associated polymorphism on regulating its mature miRNA expression was also evaluated.ResultsIn overall analyses, miR-133a-2 rs13040413 and let-7a-1 rs13293512 were related to the susceptibility to T2DM. In stratified analyses, miR-133a-2 rs13040413, let-7a-1 rs13293512 and miR-27a rs895819 showed associations with T2DM in the age ≥ 60 years subgroup. Moreover, let-7a-1 rs13293512 and miR-27a rs895819 showed associations with T2DM in male subgroup. In SNP-environmental factors interaction analyses, there were interaction effects of miR-133a-2 rs13040413 with dyslipidemia, let-7a-1 rs13293512 with smoking, and let-7a-1 rs13293512 with dyslipidemia on T2DM. In SNP-SNP interaction analyses, there were also interaction effects of miR-133a-1 rs8089787 with let-7a-1 rs13293512, and miR-133a-1 rs8089787 with let-7f rs10877887 on T2DM. Furthermore, for miR-133a-2 rs13040413, the variant T allele showed a trend toward decreased miR-133a expression in comparison with the wild C allele. For let-7a-1 rs13293512, the variant C allele expressed a lower let-7a compared to the wild T allele.ConclusionMiRNAs polymorphisms involved in the insulin signaling pathways and the interaction effects of SNP-SNP, SNP-environmental factors were related to T2DM susceptibility in a Chinese population.
| S-EPMC7897684 | biostudies-literature
Project description:Type 1 diabetes mellitus (T1DM) affects 9.5% of the population. T1DM is characterized by severe insulin deficiency that causes hyperglycemia and leads to several systemic effects. T1DM has been suggested as a risk factor for articular cartilage damage and loss, which could expedite the development of osteoarthritis (OA). OA represents a major public health challenge by affecting 300 million people globally, yet very little is known about the correlation between T1DM and OA. In this study we aimed to understand the role of T1DM in OA by evaluating whether pre-existing T1DM exacerbates the development of knee post traumatic osteoarthritis (PTOA). Here we describe the transcriptomic differences between the knee joints of STZ injected C57BL/6J mice (T1DM) and control mice
2022-03-17 | GSE198836 | GEO
Project description:Diabetes can be simply classified into type 1 diabetes mellitus and type 2 diabetes mellitus. Zinc transporter 8 (ZnT8), a novel islet autoantigen, is specifically expressed in insulin-containing secretory granules of ?-cells. Genetic studies show that the genotypes of SLC30A8 can determine either protective or diabetogenic response depending on environmental and lifestyle factors. The ZnT8 protein expression, as well as zinc content in ?-cells, was decreased in diabetic mice. Thus, ZnT8 might participate in insulin biosynthesis and release, and subsequently involved deteriorated ?-cell function through direct or indirect mechanisms in type 1 diabetes mellitus and type 2 diabetes mellitus. From a clinical feature standpoint, the prevalence of ZnT8A is gradiently increased in type 2 diabetes mellitus, latent autoimmune diabetes in adults and type 1 diabetes mellitus. The frequency and epitopes of ZnT8-specific T cells and cytokine release by ZnT8-specific T cells are also different in diabetic patients and healthy controls. Additionally, the response to ZnT8 administration is also different in type 1 diabetes mellitus and type 2 diabetes mellitus. In the present review, we summarize the literature about clinical aspects of ZnT8 in the pathogenesis of diabetes, and suggest that ZnT8 might play a different role between type 1 diabetes mellitus and type 2 diabetes mellitus.
| S-EPMC4931192 | biostudies-literature