MTNR1B Rs10830963 Research Articles

Healthy Lifestyles Modify the Association of Melatonin Receptor 1B Gene and Ischemic Stroke: A Family-Based Cohort Study in Northern China.

Limited research has reported the association between MTNR1B gene polymorphisms and ischemic stroke (IS), and there is insufficient evidence on whether adopting a healthy lifestyle can mitigate genetic risks in this context. This study aimed to investigate the associations between MTNR1B gene variants (rs10830963 and rs1387153) and IS, examining the potential effect of gene-lifestyle interactions on IS risk. Conducted in northern China, this family-based cohort study involved 5116 initially IS-free subjects. Genotype data for rs10830963 and rs1387153 in MTNR1B were collected. Eight modifiable lifestyle factors, including body mass index (BMI), smoking, alcohol consumption, dietary habits, physical activity, sedentary time, sleep duration, and chronotype, were considered in calculating healthy lifestyle scores. Multilevel Cox models were used to examine the associations between MTNR1B variants and IS. Participants carrying the rs10830963-G and rs1387153-T alleles exhibited an elevated IS risk. Each additional rs10830963-G allele and rs1387153-T allele increased the IS risk by 36% (HR = 1.36, 95%CI, 1.12-1.65) and 32% (HR = 1.32, 95%CI, 1.09-1.60), respectively. Participants were stratified into low, medium, and high healthy lifestyle score groups (1537, 2188, and 1391 participants, respectively). Genetic-lifestyle interactions were observed for rs10830963 and rs1387153 (p for interaction < 0.001). Notably, as the healthy lifestyle score increased, the effect of MTNR1B gene variants on IS risk diminished (p for trend < 0.001). This study underscores the association between the MTNR1B gene and IS, emphasizing that adherence to a healthy lifestyle can mitigate the genetic predisposition to IS.

Association of MTNR1B rs10830963 C&gt;G Polymorphism with the risk of Gestational Diabetes Mellitus: An Updated Meta-analysis

Association of MTNR1B rs10830963 C&gt;G Polymorphism with the risk of Gestational Diabetes Mellitus: An Updated Meta-analysis

Blue Light and Temperature Actigraphy Measures Predicting Metabolic Health Are Linked to Melatonin Receptor Polymorphism.

This study explores the relationship between the light features of the Arctic spring equinox and circadian rhythms, sleep and metabolic health. Residents (N = 62) provided week-long actigraphy measures, including light exposure, which were related to body mass index (BMI), leptin and cortisol. Lower wrist temperature (wT) and higher evening blue light exposure (BLE), expressed as a novel index, the nocturnal excess index (NEIbl), were the most sensitive actigraphy measures associated with BMI. A higher BMI was linked to nocturnal BLE within distinct time windows. These associations were present specifically in carriers of the MTNR1B rs10830963 G-allele. A larger wake-after-sleep onset (WASO), smaller 24 h amplitude and earlier phase of the activity rhythm were associated with higher leptin. Higher cortisol was associated with an earlier M10 onset of BLE and with our other novel index, the Daylight Deficit Index of blue light, DDIbl. We also found sex-, age- and population-dependent differences in the parametric and non-parametric indices of BLE, wT and physical activity, while there were no differences in any sleep characteristics. Overall, this study determined sensitive actigraphy markers of light exposure and wT predictive of metabolic health and showed that these markers are linked to melatonin receptor polymorphism.

Associations of the MTNR1B rs10830963 and PPARG rs1801282 variants with gestational diabetes mellitus: A meta-analysis

Associations of the MTNR1B rs10830963 and PPARG rs1801282 variants with gestational diabetes mellitus: A meta-analysis

MTNR1A and MTNR1B Gene Variants of the Melatonin Receptor and Arterial Stiffness in Persons without Arterial Hypertension.

A comparative analysis of vascular stiffness indices and the results of blood test was carried out in 85 healthy donors aged 19-64 years, carriers of polymorphic variants of type 1 and type 2 melatonin receptor genes. The associations of polymorphic markers of type 1 MTNR1A (rs34532313) and type 2 MTNR1B (rs10830963) melatonin receptor genes with parameters of vascular stiffness and blood parameters in healthy patients were studied. Genotyping was performed using allele-specific PCR. In all patients, 24-h BP monitoring with assessment of arterial stiffness was performed. Allele C homozygotes of MTNR1A differed significantly from carriers of the major T allele by elevated triglyceride, LDL, and fibrinogen levels. The major allele C of the rs10830963 polymorphic variant of the MTNR1B gene is associated with elevated LDL and triglycerides, as well as with individual differences in the elastic properties of the vascular wall in the examined subjects.

Aggregation of Genome-Wide Association Data from FinnGen and UK Biobank Replicates Multiple Risk Loci for Pregnancy Complications.

Complications endangering mother or fetus affect around one in seven pregnant women. Investigation of the genetic susceptibility to such diseases is of high importance for better understanding of the disease biology as well as for prediction of individual risk. In this study, we collected and analyzed GWAS summary statistics from the FinnGen cohort and UK Biobank for 24 pregnancy complications. In FinnGen, we identified 11 loci associated with pregnancy hypertension, excessive vomiting, and gestational diabetes. When UK Biobank and FinnGen data were combined, we discovered six loci reaching genome-wide significance in the meta-analysis. These include rs35954793 in FGF5 (p=6.1×10-9), rs10882398 in PLCE1 (p=8.9×10-9), and rs167479 in RGL3 (p=5.2×10-9) for pregnancy hypertension, rs10830963 in MTNR1B (p=4.5×10-41) and rs36090025 in TCF7L2 (p=3.4×10-15) for gestational diabetes, and rs2963457 in the EBF1 locus (p=6.5×10-9) for preterm birth. In addition to the identified genome-wide associations, we also replicated 14 out of 40 previously reported GWAS markers for pregnancy complications, including four more preeclampsia-related variants. Finally, annotation of the GWAS results identified a causal relationship between gene expression in the cervix and gestational hypertension, as well as both known and previously uncharacterized genetic correlations between pregnancy complications and other traits. These results suggest new prospects for research into the etiology and pathogenesis of pregnancy complications, as well as early risk prediction for these disorders.

Interaction between MTNR1B polymorphisms and lifestyle intervention on pregnancy outcomes

Abstract Background Interactions between polymorphisms of the melatonin receptor 1B gene (MTNR1B) and lifestyle intervention for gestational diabetes have been described. Whether these are specific for physical activity or healthy eating intervention is unknown. Objectives To assess the interaction between MTNR1B rs10830962 and rs10830963 polymorphisms and lifestyle interventions during pregnancy. Methods Women with a BMI of ≥ 29 kg/m2 (n = 436) received counseling on healthy eating (HE), physical activity (PA) or both. The control group received usual care. The analysis had a factorial design with comparison of HE versus no HE and PA versus no PA. Maternal outcomes at 24-28 weeks were gestational weight gain (GWG), maternal fasting glucose, insulin, insulin resistance (HOMA-IR), and development of GDM. Interaction between receiving either HE or PA intervention and genotypes of both rs10830962 and rs10830963 was assessed using multilevel regression analysis. Results GDM risk was increased in women homozygous for the G allele of rs10830962 or rs10830963 (OR 2.60 [95% CI 1.34, 5.06] and 2.83 [1.24, 6.47], respectively). Significant interactions between rs10830962 and interventions were found: In women homozygous for the G allele, but not in the other genotypes, the PA intervention reduced maternal fasting insulin (beta -0.16 [95%CI -0.33, 0.02], p = 0.08) and HOMA-IR (-0.17 [-0.35, 0.01], p = 0.06). In heterozygous women, HE intervention had no effect, whereas in women homozygous for the C allele, HE intervention reduced GWG (-1.6 kg [-2.4, -0.8]). Discussion In women homozygous for the risk allele of MTNR1B rs10830962, GDM risk was increased and PA intervention might be more beneficial than HE intervention for reducing maternal insulin resistance. Key messages

Development of pharmacogenomic algorithm to optimize nateglinide dose for the treatment of type 2 diabetes mellitus.

Nateglinide is a meglitinide used for the treatment of type 2 diabetes mellitus. Individual studies demonstrated the association of CYP2C9, SLCO1B1, and MTNR1B variants with the safety and efficacy of nateglinide. The current study aimed to develop a pharmacogenomic algorithm to optimize nateglinide therapy. Multiple linear regression (MLR) and classification and regression tree (CART) were used to develop a pharmacogenomic algorithm for nateglinide dosing based on the published nateglinide pharmacokinetic data on the area under the curve data (AUC) and Cmax (n = 143). CYP2C9 metabolizer phenotype, SLCO1B1, MTNR1B genotypes, and CYP2C9 inhibitor usage were used as the input variables. The results and associations were further confirmed by meta-analysis and in silico studies. The MLR models of AUC and Cmax explain 87.4% and 59% variability in nateglinide pharmacokinetics. The Bland and Altman analysis of the nateglinide dose predicted by these two MLR models showed a bias of ± 26.28mg/meal. The CART algorithm was proposed based on these findings. This model is further justified by the meta-analysis showing increased AUCs in CYP2C9 intermediate metabolizers and SLCOB1 TC and CC genotypes compared to the wild genotypes. The increased AUC in SLCO1B1 mutants is due to decreased binding affinity of nateglinide to the mutant affecting the influx of nateglinide into hepatocytes. MTNR1B rs10830963 G-allele-mediated poor response to nateglinide is attributed to increased transcriptional factor binding causing decreased insulin secretion. CYP2C9, SLCO1B1, and MTNR1B genotyping help in optimizing nateglinide therapy based on this algorithm and ensuring safety and efficacy.

Common single-nucleotide polymorphisms combined with a genetic risk score provide new insights regarding the etiology of gestational diabetes mellitus.

Few studies have constructed a genetic risk score (GRS) to predict the risk of gestaional diabetes mellitus (GDM). We tested the hypothesis that single-nucleotide polymorphisms (SNPs) confirmed for diabetes and obesity and the GRS are associated with GDM. We conducted a case-control study comprising 971 GDM cases and 1682 controls from the University of Hong Kong Shenzhen Hospital. A total of 1448 SNPs reported with type 2 diabetes (T2D), type 1 diabetes (T1D), and obesity were selected and the GRS based on SNPs associated with GDM was created. We confirmed that rs10830963 (OR=1.41,95% CI=1.25, 1.59) in MTNR1B and rs2206734 (OR=1.38, 95% CI=1.22, 1.55) in CDKAL1 were strongly associated with the risk of GDM. Compared with participants with GRS based on T2D SNPs in the low tertile, the ORs of GDM across increasing GRS tertiles were 1.63 (95% CI 1.29, 2.06) and 2.72 (95% CI 2.18, 3.38) in the middle and high tertile, respectively. The positive associations between the GRS and the risk of GDM were also observed in GRS based on obesity/waist-to-hip ratio (WHR)/body mass index (BMI) SNPs. The resulting GRS for each allele increase was significantly associated with higher glycemic indices and lower HOMA-B values for GRS based on T2D SNPs, but not for GRS based on T1D SNPs and GRS based on obesity/WHR/BMI SNPs. These findings indicate that GDM may share a common genetic background with T2D and obesity and that SNPs associated with insulin secretion defects have a vital role in the development of GDM.

Association of single nucleotide variants rs34532313 of the &lt;i&gt;MTNR1A&lt;/i&gt; gene and rs10830963 of the &lt;i&gt;MTNR1B&lt;/i&gt; gene with suicidal risk in alcohol dependence syndrome and insomnia

Background: Suicidal behaviour is the leading cause of mortality from external causes at all ages worldwide. More than a million people commit completed suicide each year. According to the World Health Organisation, 25-50% of suicide victims suffered from alcohol and other substance use disorders, 22% of all suicide deaths were attributable to alcohol use (WHO, 2014). Several papers have suggested potential associations of insomnia and increased suicide risk in patients with alcoholism. We hypothesise that mutations in melatonin receptor genes may be associated with suicide risk in patients with alcoholism.Methods. The Insomnia Severity Index (ISI) was used as a tool to assess the presence and severity of insomnia. The Columbia Suicide Severity Rating Scale (C-SSRS) was used as a method to examine suicidal behavior. Genotyping of MTNR1A (rs34532313), MTNR1B (rs10830963) genes was performed using real-time polymerase chain reaction (RT-PCR). A comparative genetic study of two groups of patients was carried out: the first group, patients with alcohol dependence syndrome (F10.2); the second group, patients with alcohol dependence syndrome (F10.2) and insomnia, which persisted 7-14 days after starting alcohol withdrawal therapy.Results. Suicidal thoughts and a history of auto-aggressive behaviour were more common in subjects with insomnia in the post-withdrawal period. Carriers of the TT genotype of the MTNR1A gene (rs34532313) were more likely to have suicidal thoughts and a history of suicide attempts in a genetic study of patients with insomnia.Conclusions. Our study found that the TT genotype of the MTNR1A gene (rs34532313) is a genetic marker of suicidal behaviour risk in patients with insomnia in the post-withdrawal period. However, the same pattern was not observed in patients without insomnia.

The role of MTNR1B polymorphism on circadian rhythm-related cancer: A UK Biobank cohort study.

A common G risk allele in the melatonin receptor 1B (MTNR1B, rs10830963) gene has been associated with altered melatonin signaling and secretion. Given that melatonin possesses anticancerogenic properties, we hypothesized that breast and prostate cancer risks vary by rs10830963 genotype. A total of 216 702 participants from the UK Biobank without cancer at baseline (aged 56.4 ± 8.0 years, 50.79% female) were included. Multivariable Cox regression adjusting for known risk factors for breast or prostate cancer was used to estimate the independent effects of the rs10830963 SNP and chronotype on cancer risk. Over a median follow‐up of 8 years, 2367 (2.15% of women) incidences of breast cancer and 2866 (2.69% of men) incidences of prostate cancer were documented in females and males, respectively. rs10830963 genotype is not associated with cancer risk independently (female P trend = .103, male P trend = .281). A late chronotype is associated with breast cancer risk in females (P trend = .014), but not prostate cancer risk in males (P trend = .915). Further stratification analysis revealed that the rs10830963 genotype is associated with a breast cancer risk in females with moderate evening chronotype (P trend = .001) and late chronotype is associated with breast cancer risk in females who carry rs10830963 G risk allele (P trend = .015). Our study suggests that having a late chronotype might increase the risk of breast cancer among females, while the effect of MTNR1B rs10830963 genotype on breast cancer risk is mediated by chronotype.

An early prediction model for gestational diabetes mellitus based on genetic variants and clinical characteristics in China

ObjectivesTo evaluate the influence of genetic variants and clinical characteristics on the risk of gestational diabetes mellitus (GDM) and to construct and verify a prediction model of GDM in early pregnancy.MethodsFour hundred seventy five women with GDM and 487 women without, as a control, were included to construct the prediction model of GDM in early pregnancy. Both groups had complete genotyping results and clinical data. They were randomly divided into a trial cohort (70%) and a test cohort (30%). Then, the model validation cohort, including 985 pregnant women, was used for the external validation of the GDM early pregnancy prediction model.ResultsWe found maternal age, gravidity, parity, BMI and family history of diabetes were significantly associated with GDM (OR > 1; P < 0.001), and assisted reproduction was a critical risk factor for GDM (OR = 1.553, P = 0.055). MTNR1B rs10830963, C2CD4A/B rs1436953 and rs7172432, CMIP rs16955379 were significantly correlated with the incidence of GDM (AOR > 1, P < 0.05). Therefore, these four genetic susceptible single nucleotide polymorphisms (SNPs) and six clinical characteristics were included in the construction of the GDM early pregnancy prediction model. In the trial cohort, a predictive model of GDM in early pregnancy was constructed, in which genetic risk score was independently associated with GDM (AOR = 2.061, P < 0.001) and was the most effective predictor with the exception of family history of diabetes. The ROC-AUC of the prediction model was 0.727 (95% CI 0.690–0.765), and the sensitivity and specificity were 69.9% and 64.0%, respectively. The predictive power was also verified in the test cohort and the validation cohort.ConclusionsBased on the genetic variants and clinical characteristics, this study developed and verified the early pregnancy prediction model of GDM. This model can help screen out the population at high-risk for GDM in early pregnancy, and lifestyle interventions can be performed for them in a timely manner in early pregnancy.

Night Shift Work, MTNR1B rs10830963 Polymorphism, and Prostate Cancer Risk: Findings from a Prospective, Population-Based Study.

The association between night shift work and prostate cancer is controversial. Evidence shows that genetic and environmental factors both contribute to the development of prostate cancer. It is well known that melatonin plays a protective role in prostate cancer. Melatonin receptor 1B gene (MTNR1B) rs10830963 influences the dynamics of melatonin secretion, and night shift work, which disrupts our internal circadian rhythms, also dysregulates the production of melatonin. Therefore, we aimed to examine the interaction between night shift work and rs10830963 polymorphism on prostate cancer. This is a prospective cohort study based on UK Biobank that included 133,416 employed male participants. Exposures included night shift work and rs10830963 polymorphism. The primary outcome was the incidence of prostate cancer. Cox regression analysis was used to estimate the association of night shift work and MTNR1B rs10830963 with prostate cancer. A significant interaction was found between night shift work and MTNR1B rs10830963 on the incidence of prostate cancer (P = 0.009). Among non-night shift workers, rs10830963 polymorphism was not significantly associated with the risk of prostate cancer. Among night shift workers, compared with CC carriers, GC carriers had a significantly lower risk of prostate cancer [HR: 0.69; 95% confidence interval (CI): 0.51-0.93], and similar associations were more evident for GG carriers (HR: 0.33; 95% CI: 0.15-0.75). Compared with MTNR1B rs10830963 CC, carrying allele G may reduce the risk of prostate cancer when exposed to night shift work. These results suggest that rs10830963 G carriers may have a lower risk of prostate cancer when taking night shifts.

Melatonin, circadian rhythms and glaucoma: current perspective.

Melatonin, circadian rhythms and glaucoma: current perspective.

The connection of polymorphism and diurnal changes of the biological clock gene expression with the risk of progression of primary open-angle glaucoma

The purpose of this work is to study the connection betweengenetic factors (polymorphism and expression of key genes of the biological clock (KGBC), key genes controlled by KGBC, melatonin receptors) and the diurnal oscillation of melatonin in patients with stable and progressing primary open-angle glaucoma. Materials and methods. The study involved 115 patients aged 53–86 (averagely, 68.8 ± 7.9 years) with stable and progressive glaucoma. All patients underwent primary ophthalmological examination, tested for diurnal body temperature profile, intraocular pressure (IOP), melatonin (by the DLMO protocol) and were typed for key genes of the biological clock using the real-time polymerase chain reaction. We studied the sleep phase shift to later hours in carriers of the G-allele of the melatonin receptor gene during the progression of glaucoma. Results. The study of the clinical and genotypic features of the POAG course revealed phasal shifts of the circadian rhythms of body temperature, IOP, salivary melatonin levels and sleep phases which contributed to the progression of glaucomatous optic neuropathy. Certain polymorphic variants of genes contribute to individual frequent manifestations of desynchronosis. The clock rs1801260 and MTNR1B rs10830963 gene polymorphism was found to be related to disturbances in melatonin production and sleep phase. Conclusion. Complex manifestations of circadian desynchronization accompanying the progressive course of glaucoma are the late phase of rhythms and a decrease in sleep duration, body temperature, salivary melatonin and IOP, internal desynchronization between IOP and body temperature, IOP and sleep, evening dyslipidemia. The revealed patterns open up prospects for future studies of the relationship between polymorphism and daily changes of the expression of key genes in the biological clock with the risk of progression of primary open angle glaucoma.

Association of alcohol withdrawal severity with MTNR1A (rs34532313) and MTNR1B (rs10830963) genes polymorphisms

Alcohol withdrawal is the most threatening condition encountered in patients with alcohol use disorder. Our study aimed to investigate the association of alcohol withdrawal severity with polymorphic variants in melatonin receptor genes. Methods. The clinical study was carried out on the basis of the Republican Narcological Dispensary №1 in Ufa and the Republican Narcological Dispensary №2 in Sterlitamak. Genetic analysis was performed at the Department of Personalised Psychiatry and Neurology at the V.M. Bekhterev Research Centre, Saint Petersburg. The final sample consisted of 307 subjects. Results. Carriers of the TT genotype of the MTNR1A gene (rs34532313) were found to have less hypertension during alcohol withdrawal than carriers of the other genotypes. In comparison, carriers of the GG genotype of the MTNR1B gene (rs10830963) experienced more symptoms than other genotypes: paroxysmal sweating, visual hallucinations, anxiety, and overall CIWA-Ar score. Conclusions. Thus, it can be concluded that the TT genotype of MTNR1A gene (rs34532313) is associated with a lower risk of hypertension during alcohol withdrawal compared to carriers of other gene genotypes. The GG genotype of MTNR1B gene (rs10830963) is associated with severe withdrawal. In general, it can be concluded that melatonin receptors are involved in the pathogenesis of alcohol withdrawal and the severe of some of its symptoms.

Associations of molecular genetic predictors of type 2 diabetes mellitus with hyperglycemia in extremely low birth weight infants

Hyperglycemia in premature newborns is an independent risk factor for death, so blood glucose testing is widely used in the practice of neonatal intensive care units.Objective: to evaluate the associations of the frequency of carriage of allelic variants of polymorphic loci of genes predisposing to type 2 diabetes mellitus in newborns with extremely low body weight and hyperglycemia.Methods. The study design is prospective, controlled, single – center, non-randomized. Genomic DNA samples were studied in newborn infants with extremely low body weight (ELBW) (n = 105). Previously, we compared the distribution of allele frequencies of the studied genes between a group of newborns with ELBW and a population sample of adults (control). Then, the distribution of allele frequencies of the genes was compared depending on the presence of hyperglycemia in newborns with ELBW. For the analysis, loci with already known association with the development of type 2 diabetes mellitus were selected ‒ ADRB2 (rs1042713) and (rs1042714), ADRB3 (rs4994), GNB3 (rs5443), PPARA (rs4253778), PPARD (rs2016520), TCF7L2_IVS3 (rs7903146) and TCF7L2_IVS4 (rs12255372), PPARGC1A (rs8192678), MTHFR (rs1801131), PPARG (rs1801282), MTNR1B (rs10830963), SIRT1 (rs7069102).Results. In newborns with ELBW, we found a more frequent occurrence of the mutant allele A of the polymorphic locus rs8192678 in the PPARGC1A gene and the allele C of the polymorphic locus rs4253778 in the PPARA gene, in contrast to the adult population sample. But in newborns with ELBW, hyperglycemia is most likely associated with the carrier of the allele C rs1801282 of the PPARG gene (χ2 = 18.972, p &lt; 0.001) and the allele T rs7903146 in the TCF7L2 gene (χ2 = 11.496, p &lt; 0.001).Conclusions. The carriage of the allele С rs1801282 of the PPARG gene is characterized by the presence of a strong conjugation with hyperglycemia in newborns with extremely low body weight. It is desirable to monitor the level of glycemia in the conditions of neonatal intensive care units, taking into account the carriage of genes predisposing to hyperglycemia.

Association of polymorphic variants of genes &lt;i&gt;(HTR2A, MTNR1A, MTNR1B, CLOCK, DRD2)&lt;/i&gt; and insomnia in alcohol dependence syndrome

The majority of patients with alcohol dependence syndrome suffer from sleep disorders, particularly insomnia, associated with a number of critical clinical aspects, increased suicide risk, anxiety and depression. The authors of relevant publications indicate associations between polymorphic melatonin genes and melatonin metabolism and symptoms of sleep disorders. However, the literature review failed to reveal any studies on the role of genetic polymorphism of circadian rhythm regulators in sleep disorders in patients with alcohol dependence.Objective: to determine the associations of polymorphic variants of genes HTR2A, MTNR1A, MTNR1B, CLOCK, DRD2 with sleep disorders risk in alcohol dependence syndrome.Patients and methods. 307 patients with alcohol dependence syndrome were screened, including 61 women (21%) and 246 (79%) men (mean age – 41.92±7.9 years). The presence and severity of sleep disorders were assessed by the Insomnia Severity Index. In addition, 10 ml of venous blood sample was obtained from all participants. Genotyping of single nucleotide variants of HTR2A (rs6313), MTNR1A (rs34532313), MTNR1B (rs10830963), CLOCK (rs1801260), DRD2 (rs1800497) genes was performed using real-time polymerase chain reaction. Statistical analysis of the data was conducted using parametric and nonparametric methods.Results and discussion. The carriage of the *G allele of the polymorphic variant of the MTNR1B (rs10830963) gene, and its genotypes are associated with a greater risk of insomnia than the carriage of *С/*С genotype. The carriage of the *С allele of the polymorphic variant of the CLOCK (rs1801260) gene, as well as the *С/*Т genotype, are associated with the presence of sleep disorders. No associations between polymorphic variants of the HTR2A (rs6313), DRD2 (rs1800497) genes and insomnia risk were detected in patients with alcohol dependence syndrome.Conclusion. The found associations reveal prospects for future research on melatonin's role in the pathophysiology of sleep disorders in patients with alcohol dependence and pathogenetic therapy for insomnia.

Association Association of genetic variant of OXTR (rs53576) and MTNR-1B (rs10830963 and rs1387153) with symptoms of stress in Pakistani women with Gestational Diabetes.

Background: Pregnancy continues to be an event full of risks, complications and adverse outcomes for women despite advanced clinical and diagnostic methods and treatment options available in medicine. Diabetes, as a multifactorial and complex disease, is a possible outcome of a blend of numerous genetic variants of differing scarcities. The exact etiology of gestational diabetes mellitus (GDM) is unclear; however, the interaction of genetic and environmental factors, especially the genetic variants identified as the genetic loci for type 2 diabetes as candidate genes for GDM.&#x0D; Methodology: It will be a case-control study with a genetic analysis of single nucleotide polymorphisms (SNPs) of candidate genes expressed using real-time PCR with sequencing. The study will also evaluate the primer sequence of SNPs.&#x0D; Discussion: We will be able to share the findings after the completion of our research. The results of this study will able helpful in addressing the psycho-physiological needs of women with GDM, which may also be used to devise strategies to benefit the sustainable long-term behavioural change following the affected pregnancy.

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

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.