Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Increased Risk of Myocardial Infarction Among Patients With Type 2 Diabetes Who Carry the Common rs10830963 Variant in the MTNR1B Gene.

ABSTRACT:

Objective

The common MTNR1B single nucleotide polymorphism rs10830963 associates with risk of type 2 diabetes (T2D). Here, we examine the association between this gene variant and the risk of myocardial infarction (MCI) among patients with T2D. MCI is a main cause of death and disability among such individuals.

Research design and methods

Data from the UK Biobank cohort were used in order to examine the association between rs10830963 and incidence of MCI (fatal and nonfatal) among 13,655 participants with probable T2D during a follow-up period of 6.8 years.

Results

Assuming an additive genetic model, a positive association was found between the rs10830963 variant in the MTNR1B gene and the risk for incident MCI during the 6.8-year follow-up (adjusted hazard ratio per G allele 1.19 [95% CI 1.02, 1.40], P = 0.03).

Conclusions

The rs10830963 polymorphism may be a useful genetic marker for MCI in patients with T2D.

SUBMITTER: Tan X

PROVIDER: S-EPMC7440907 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Increased Risk of Myocardial Infarction Among Patients With Type 2 Diabetes Who Carry the Common rs10830963 Variant in the <i>MTNR1B</i> Gene.

Tan Xiao X Benedict Christian C

Diabetes care 20200702 9

<h4>Objective</h4>The common <i>MTNR1B</i> single nucleotide polymorphism rs10830963 associates with risk of type 2 diabetes (T2D). Here, we examine the association between this gene variant and the risk of myocardial infarction (MCI) among patients with T2D. MCI is a main cause of death and disability among such individuals.<h4>Research design and methods</h4>Data from the UK Biobank cohort were used in order to examine the association between rs10830963 and incidence of MCI (fatal and nonfatal ...[more]

PMID: 32616615

Similar Datasets

Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion.

Project description:Genome-wide association studies have shown that variation in MTNR1B (melatonin receptor 1B) is associated with insulin and glucose concentrations. Here we show that the risk genotype of this SNP predicts future type 2 diabetes (T2D) in two large prospective studies. Specifically, the risk genotype was associated with impairment of early insulin response to both oral and intravenous glucose and with faster deterioration of insulin secretion over time. We also show that the MTNR1B mRNA is expressed in human islets, and immunocytochemistry confirms that it is primarily localized in beta cells in islets. Nondiabetic individuals carrying the risk allele and individuals with T2D showed increased expression of the receptor in islets. Insulin release from clonal beta cells in response to glucose was inhibited in the presence of melatonin. These data suggest that the circulating hormone melatonin, which is predominantly released from the pineal gland in the brain, is involved in the pathogenesis of T2D. Given the increased expression of MTNR1B in individuals at risk of T2D, the pathogenic effects are likely exerted via a direct inhibitory effect on beta cells. In view of these results, blocking the melatonin ligand-receptor system could be a therapeutic avenue in T2D.

| S-EPMC3725650 | biostudies-literature

Evaluation of the effect of MTNR1B rs10830963 gene variant on the therapeutic efficacy of nateglinide in treating type 2 diabetes among Chinese Han patients.

Project description:Genetic polymorphisms in the MTNR1B gene is associated with type 2 diabetes mellitus (T2DM); however, there is no evidence about its impact on the therapeutic efficacy of nateglinide. This prospective case-control study was designed to investigate the effect of MTNR1B rs10830963 gene variant on the therapeutic efficacy of nateglinide in treating T2DM. We genotyped untreated T2DM patients (N = 200) and healthy controls (N = 200) using the method of the high resolution of melting curve (HRM). Newly diagnosed T2DM patients (n = 60) with CYP2C9*1 and SLCO1B1 521TT genotypes were enrolled and given oral nateglinide (360 mg/d) for 8 weeks. The outcome was measured by collecting the venous blood samples before and at the 8th week of the treatment. The risk G allelic frequency of MTNR1B rs10830963 was higher in T2DM patients than the healthy subjects (P < 0.05). Post 8-week of treatment, newly diagnosed T2DM patients showed a less reduction in fasting plasma glucose levels and less increase in the carriers of genotype CG + GG at rs10830963 when compared with the CC genotype (P < 0.05). MTNR1B rs10830963 polymorphism was associated with the therapeutic efficacy of nateglinide in T2DM patients. Also, the CC homozygotes had a better effect than G allele carriers.Trial registration Chinese Clinical Trial Register ChiCTR13003536, date of registration: May 14, 2013.

| S-EPMC8196487 | biostudies-literature

Common type 2 diabetes risk variant in MTNR1B worsens the deleterious effect of melatonin on glucose tolerance in humans.

Project description:AimsThe common MTNR1B genetic variant rs10830963 is associated with an increased risk of type 2 diabetes (T2D). To date, no experimental study has tested the effect of the MTNR1B variant on glucose metabolism in humans during exposure of the melatonin receptors to their ligand. The aim of this study was to investigate whether this MTNR1B variant influenced the effect of melatonin (5mg) on glucose tolerance assessed by an oral glucose tolerance test (OGTT; 75 g) at different times of the day (morning and evening) as compared to a placebo.MethodsSeventeen normoglycemic women (24 ± 6 years; BMI 23.0 ± 3.3 kg/m(2)) completed the study (11 carriers of the risk allele [CG] and 6 noncarriers [CC]).ResultsThe effect of melatonin on glucose tolerance depended on the genotype. In the morning, the effect of melatonin (melatonin-placebo) on the glucose area under the curve (AUC) above baseline differed significantly (P=0.036) between the carriers and noncarriers. This effect of melatonin in the carriers was six times as large as that in the noncarriers. The MTNR1B SNP explained over one-quarter (26%) of the inter-individual differences in the effect of melatonin on glucose AUC. However, in the evening, the effect of melatonin on glucose AUC of the carriers and noncarriers did not differ significantly (P>0.05).ConclusionsMTNR1B rs10830963 risk variant worsens the effect of melatonin on glucose tolerance, suggesting the importance of genotyping and personalized recommendations, especially in people consuming food when melatonin levels are elevated. Large-scale studies in vulnerable populations are necessary to translate these results into real-world, clinically relevant recommendations.

| S-EPMC4856010 | biostudies-literature

Impact of Common Diabetes Risk Variant in MTNR1B on Sleep, Circadian, and Melatonin Physiology.

Project description:The risk of type 2 diabetes (T2D) is increased by abnormalities in sleep quantity and quality, circadian alignment, and melatonin regulation. A common genetic variant in a receptor for the circadian-regulated hormone melatonin (MTNR1B) is associated with increased fasting blood glucose and risk of T2D, but whether sleep or circadian disruption mediates this risk is unknown. We aimed to test if MTNR1B diabetes risk variant rs10830963 associates with measures of sleep or circadian physiology in intensive in-laboratory protocols (n = 58-96) or cross-sectional studies with sleep quantity and quality and timing measures from self-report (n = 4,307-10,332), actigraphy (n = 1,513), or polysomnography (n = 3,021). In the in-laboratory studies, we found a significant association with a substantially longer duration of elevated melatonin levels (41 min) and delayed circadian phase of dim-light melatonin offset (1.37 h), partially mediated through delayed offset of melatonin synthesis. Furthermore, increased T2D risk in MTNR1B risk allele carriers was more pronounced in early risers versus late risers as determined by 7 days of actigraphy. Our results provide the surprising insight that the MTNR1B risk allele influences dynamics of melatonin secretion, generating a novel hypothesis that the MTNR1B risk allele may extend the duration of endogenous melatonin production later into the morning and that early waking may magnify the diabetes risk conferred by the risk allele.

| S-EPMC4878414 | biostudies-literature

Myocardial Infarction Susceptibility and the <i>MTNR1B</i> Polymorphisms.

Project description:Melatonin is a circadian hormone with antioxidant properties that protects against myocardial ischemia-reperfusion injury. Genetic variations of the melatonin receptor 1B gene (MTNR1B) play an important role in the development of type 2 diabetes, a risk factor for cardiovascular diseases. Accordingly, MTNR1B polymorphisms are crucial in numerous disorders of the cardiovascular system. Therefore, the aim of the present study was to investigate a possible association of MTNR1B polymorphisms with chronotype and susceptibility to myocardial infarction. The present case-control study included 199 patients with myocardial infarction (MI) (57% men) and 198 control participants (52% men) without previous cardiovascular diseases who underwent genotyping for the MTNR1B polymorphisms rs10830963, rs1387153, and rs4753426 from peripheral blood samples. Chronotype was determined using the Morningness-Eveningness Questionnaire (MEQ). As estimated by the chi-square test, no significant association was found in the distribution of alleles and genotypes between myocardial infarction patients and controls. In addition, there was no association between MTNR1B polymorphisms and chronotype in MI patients. As some previous studies have shown, the present negative results do not exclude the role of the MTNR1B polymorphisms studied in the development of myocardial infarction. Rather, they may indicate that MTNR1B polymorphisms are a minor risk factor for myocardial infarction.

| S-EPMC10380655 | biostudies-literature

G-allele of intronic rs10830963 in MTNR1B confers increased risk of impaired fasting glycemia and type 2 diabetes through an impaired glucose-stimulated insulin release: studies involving 19,605 Europeans.

Project description:OBJECTIVE:Genome-wide association studies have identified several variants within the MTNR1B locus that are associated with fasting plasma glucose (FPG) and type 2 diabetes. We refined the association signal by direct genotyping and examined for associations of the variant displaying the most independent effect on FPG with isolated impaired fasting glycemia (i-IFG), isolated impaired glucose tolerance (i-IGT), type 2 diabetes, and measures of insulin release and peripheral and hepatic insulin sensitivity. RESEARCH DESIGN AND METHODS:We examined European-descent participants in the Inter99 study (n = 5,553), in a sample of young healthy Danes (n = 372), in Danish twins (n = 77 elderly and n = 97 young), in additional Danish type 2 diabetic patients (n = 1,626) and control subjects (n = 505), in the Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study (n = 4,656), in the North Finland Birth Cohort 86 (n = 5,258), and in the Haguenau study (n = 1,461). RESULTS:The MTNR1B intronic variant, rs10830963, carried most of the effect on FPG and showed the strongest association with FPG (combined P = 5.3 x 10(-31)) and type 2 diabetes. The rs10830963 G-allele increased the risk of i-IFG (odds ratio [OR] 1.64, P = 5.5 x 10(-11)) but not i-IGT. The G-allele was associated with a decreased insulin release after oral and intravenous glucose challenges (P < 0.01) but not after injection of tolbutamide. In elderly twins, the G-allele associated with hepatic insulin resistance (P = 0.017). CONCLUSIONS:The G-allele of MTNR1B rs10830963 increases risk of type 2 diabetes through a state of i-IFG and not through i-IGT. The same allele associates with estimates of beta-cell dysfunction and hepatic insulin resistance.

| S-EPMC2682679 | biostudies-literature

The MTNR1B rs10830963 Variant in Interaction with Pre-Pregnancy BMI is a Pharmacogenetic Marker for the Initiation of Antenatal Insulin Therapy in Gestational Diabetes Mellitus.

Project description:The rs10830963 variant of the Melatonin Receptor 1B (MTNR1B) gene is associated with the development of gestational diabetes mellitus (GDM). We hypothesized that carrying the rs10830963/G risk allele had effect on antenatal insulin therapy (AIT) initiation in GDM in a body mass index (BMI)-dependent manner. Design: In this post hoc analysis the MTNR1B rs10830963 genotype and the clinical data of 211 Caucasian GDM patients were assessed. As a first step, a pre-pregnancy BMI threshold was determined where the effect of MTNR1B rs10830963/G allele carrying on AIT initiation was the most significant using logistic regression. Maternal age adjusted real-life odds ratios (OR) values were calculated. The chi-square test was also used to calculate the p value and 10.000 bootstrap simulations were performed in each case to re-assess the statistical power and the OR. Carrying the MTNR1B rs10830963/G allele increased the odds of AIT initiation (OR = 5.2, p = 0.02 [χ² test], statistical power = 0.53) in GDM patients with pre-pregnancy BMI ≥ 29 kg/m². The statistical power reached 0.77, when the pre-pregnancy BMI cutoff of 27 kg/m² was used and the genetic effect on AIT initiation was still significant, but only using the logistic regression model. Carrying the MTNR1B rs10830963/G risk allele-in interaction with pre-pregnancy BMI-is likely be considered as a candidate pharmacogenetic marker of antenatal insulin therapy initiation and should be further assessed in precision medicine trials in GDM.

| S-EPMC6321391 | biostudies-literature

Association Study with 77 SNPs Confirms the Robust Role for the rs10830963/G of MTNR1B Variant and Identifies Two Novel Associations in Gestational Diabetes Mellitus Development.

Project description:ContextGenetic variation in human maternal DNA contributes to the susceptibility for development of gestational diabetes mellitus (GDM).ObjectiveWe assessed 77 maternal single nucleotide gene polymorphisms (SNPs) for associations with GDM or plasma glucose levels at OGTT in pregnancy.Methods960 pregnant women (after dropouts 820: case/control: m99'WHO: 303/517, IADPSG: 287/533) were enrolled in two countries into this case-control study. After genomic DNA isolation the 820 samples were collected in a GDM biobank and assessed using KASP (LGC Genomics) genotyping assay. Logistic regression risk models were used to calculate ORs according to IADPSG/m'99WHO criteria based on standard OGTT values.ResultsThe most important risk alleles associated with GDM were rs10830963/G of MTNR1B (OR = 1.84/1.64 [IADPSG/m'99WHO], p = 0.0007/0.006), rs7754840/C (OR = 1.51/NS, p = 0.016) of CDKAL1 and rs1799884/T (OR = 1.4/1.56, p = 0.04/0.006) of GCK. The rs13266634/T (SLC30A8, OR = 0.74/0.71, p = 0.05/0.02) and rs7578326/G (LOC646736/IRS1, OR = 0.62/0.60, p = 0.001/0.006) variants were associated with lower risk to develop GDM. Carrying a minor allele of rs10830963 (MTNR1B); rs7903146 (TCF7L2); rs1799884 (GCK) SNPs were associated with increased plasma glucose levels at routine OGTT.ConclusionsWe confirmed the robust association of MTNR1B rs10830963/G variant with GDM binary and glycemic traits in this Caucasian case-control study. As novel associations we report the minor, G allele of the rs7578326 SNP in the LOC646736/IRS1 region as a significant and the rs13266634/T SNP (SLC30A8) as a suggestive protective variant against GDM development. Genetic susceptibility appears to be more preponderant in individuals who meet both the modified 99'WHO and the IADPSG GDM diagnostic criteria.

| S-EPMC5224877 | biostudies-literature

Common genetic variation near melatonin receptor MTNR1B contributes to raised plasma glucose and increased risk of type 2 diabetes among Indian Asians and European Caucasians.

Project description:Fasting plasma glucose and risk of type 2 diabetes are higher among Indian Asians than among European and North American Caucasians. Few studies have investigated genetic factors influencing glucose metabolism among Indian Asians.We carried out genome-wide association studies for fasting glucose in 5,089 nondiabetic Indian Asians genotyped with the Illumina Hap610 BeadChip and 2,385 Indian Asians (698 with type 2 diabetes) genotyped with the Illumina 300 BeadChip. Results were compared with findings in 4,462 European Caucasians.We identified three single nucleotide polymorphisms (SNPs) associated with glucose among Indian Asians at P < 5 x 10(-8), all near melatonin receptor MTNR1B. The most closely associated was rs2166706 (combined P = 2.1 x 10(-9)), which is in moderate linkage disequilibrium with rs1387153 (r(2) = 0.60) and rs10830963 (r(2) = 0.45), both previously associated with glucose in European Caucasians. Risk allele frequency and effect sizes for rs2166706 were similar among Indian Asians and European Caucasians: frequency 46.2 versus 45.0%, respectively (P = 0.44); effect 0.05 (95% CI 0.01-0.08) versus 0.05 (0.03-0.07 mmol/l), respectively, higher glucose per allele copy (P = 0.84). SNP rs2166706 was associated with type 2 diabetes in Indian Asians (odds ratio 1.21 [95% CI 1.06-1.38] per copy of risk allele; P = 0.006). SNPs at the GCK, GCKR, and G6PC2 loci were also associated with glucose among Indian Asians. Risk allele frequencies of rs1260326 (GCKR) and rs560887 (G6PC2) were higher among Indian Asians compared with European Caucasians.Common genetic variation near MTNR1B influences blood glucose and risk of type 2 diabetes in Indian Asians. Genetic variation at the MTNR1B, GCK, GCKR, and G6PC2 loci may contribute to abnormal glucose metabolism and related metabolic disturbances among Indian Asians.

| S-EPMC2768158 | biostudies-literature

A common variant in the MTNR1b gene is associated with increased risk of impaired fasting glucose (IFG) in youth with obesity.

Project description:ObjectiveTo explore the role of MTNR1B rs10830963 and G6PC2 rs560887 variants in the pathogenesis of impaired fasting glucose (IFG) in obese adolescents.MethodsA total of 346 Caucasians, 218 African-Americans, and 217 Hispanics obese children and adolescents underwent an oral glucose tolerance test (OGTT) and 518 underwent the evaluation of insulin secretion by the oral minimal model (OMM). Also, 274 subjects underwent a second OGTT after 3.0 ± 2.1 years.ResultsThe MTNR1B rs10830963 variant was associated with higher fasting glucose levels and lower dynamic beta-cell response in Caucasians and Hispanics (P < 0.05) and conferred an increased risk of showing IFG to Caucasians (P = 0.05), African-Americans (P = 0.0066), and Hispanics (P = 0.024). Despite the association between the G6PC2 rs560887 and higher fasting glucose levels (P < 0.05), there was no association between this variant and IFG at baseline or at follow-up (all P > 0.10).ConclusionsIt has been shown for the first time in obese youth that the MTNR1B variant is associated with an increased risk of IFG.

| S-EPMC4414047 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data