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

Abstract Background: Several studies have shown the association of polymorphisms in the MTNR1B gene with type 2 diabetes mellitus (T2DM). However, there is no evidence about the impacts of its genetic polymorphism on the therapeutic efficacy of nateglinide. Therefore, this prospective case-control study was designed to investigate the effect of MTNR1B rs10830963 gene polymorphism on the therapeutic efficacy of nateglinide in treating T2DM. Methods: We genotyped 200 healthy subjects using the method of the high resolution of melting curve (HRM). A total of 60 T2DM patients were enrolled and given nateglinide (360 mg/d) for 8 weeks orally who had the same genotypes CYP2C9*1 and SLCO1B1 521TT respectively. The outcome was measured by collecting the venous blood samples before and at the 8th week of the treatment. Also, anthropometric measurements, glucose, and lipid metabolism were determined before and after the nateglinide treatment. Results: It was found that the risk G allelic frequency of MTNR1B rs10830963 was higher in T2DM patients when compared with the healthy subjects (P<0.05). 60 newly diagnosed patients with type 2 diabetes after completing the eight weeks treatment came for the follow-up visit and showed a reduction in fasting plasma glucose (FPG) levels with an increase in homeostasis model assessment for β cell HOMA-β in the carriers of genotype CG + GG at rs10830963, when compared with the wild-type CC (P <0.05). Conclusion: Thus, it was found that the 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: This study was registered in the Chinese Clinical Trial Register (No. ChiCTR-CCC13003536).

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

10.21203/rs.2.14474/v2 ◽

2019 ◽

Author(s):

jinfang song ◽

Mingzhu Zhang ◽

Jiang Ni ◽

Tao Wang ◽

Yi-Qing Zhao

Keyword(s):

Type 2 Diabetes ◽

Gene Polymorphism ◽

Therapeutic Efficacy ◽

Healthy Subjects ◽

Venous Blood ◽

Melting Curve ◽

Treatment Result ◽

Model Assessment ◽

Newly Diagnosed

Abstract Background: Several studies have shown the association of polymorphisms in the MTNR1B gene with type 2 diabetes mellitus (T2DM). However, there is no evidence about the impacts of its genetic polymorphism on the therapeutic efficacy of nateglinide. Therefore, this prospective case-control study was designed to investigate the effect of MTNR1B rs10830963 gene polymorphism on the therapeutic efficacy of nateglinide in treating T2DM. Methods: We genotyped 200 healthy subjects using the method of the high resolution of melting curve (HRM). A total of 60 newly diagnosed T2DM patients were enrolled and given nateglinide (360 mg/d) for 8 weeks orally who had the same genotypes CYP2C9*1 and SLCO1B1 521TT respectively. The outcome was measured by collecting the venous blood samples before and at the 8th week of the treatment. Also, anthropometric measurements, glucose, and lipid metabolism were determined before and after the nateglinide treatment. Result: It was found that the risk G allelic frequency of MTNR1B rs10830963 was higher in T2DM patients when compared with the healthy subjects (P<0.05). A total of 60 newly diagnosed patients with type 2 diabetes after completing the eight weeks treatment came for the follow-up visit and showed a less reduction in fasting plasma glucose (FPG) levels with a less increase in homeostasis model assessment for β cell HOMA-β in the carriers of G allele at rs10830963, when compared with the wild-type CC (P <0.05). Conclusion: Thus, it was found that the 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.

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

10.21203/rs.2.14474/v3 ◽

2021 ◽

Author(s):

Jin-Fang Song ◽

Jie Zhang ◽

Ming-Zhu Zhang ◽

Jiang Ni ◽

Tao Wang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Gene Polymorphism ◽

Therapeutic Efficacy ◽

Venous Blood ◽

Melting Curve ◽

Allelic Frequency ◽

Newly Diagnosed ◽

Chinese Han ◽

Glucose Levels

Abstract 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 polymorphism 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.

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

BMC Medical Genomics ◽

10.1186/s12920-021-01004-y ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Jin-Fang Song ◽

Jie Zhang ◽

Ming-Zhu Zhang ◽

Jiang Ni ◽

Tao Wang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Therapeutic Efficacy ◽

Venous Blood ◽

Melting Curve ◽

Allelic Frequency ◽

Gene Variant ◽

Newly Diagnosed ◽

Chinese Han ◽

Glucose Levels

AbstractGenetic 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.

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The KCNJ11 E23K gene polymorphism and type 2 diabetes mellitus in the Chinese Han population: a meta-analysis of 6,109 subjects

Molecular Biology Reports ◽

10.1007/s11033-012-2042-9 ◽

2012 ◽

Vol 40 (1) ◽

pp. 141-146 ◽

Cited By ~ 16

Author(s):

Yan-yan Li

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Gene Polymorphism ◽

Meta Analysis ◽

Chinese Han Population ◽

Chinese Han ◽

Han Population

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The Impacts ofSLC22A1rs594709 andSLC47A1rs2289669 Polymorphisms on Metformin Therapeutic Efficacy in Chinese Type 2 Diabetes Patients

International Journal of Endocrinology ◽

10.1155/2016/4350712 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 10

Author(s):

Di Xiao ◽

Yu Guo ◽

Xi Li ◽

Ji-Ye Yin ◽

Wei Zheng ◽

...

Keyword(s):

Type 2 Diabetes ◽

Therapeutic Efficacy ◽

Healthy Subjects ◽

Allele Frequencies ◽

Metformin Treatment ◽

Newly Diagnosed ◽

Genotype Frequencies ◽

Metformin Monotherapy ◽

Significant Difference

Background. We aimed to investigate the distributive characteristics ofSLC22A1rs594709 andSLC47A1rs2289669 polymorphisms and their influence on metformin efficacy in Chinese T2DM patients.Methods. The distributions ofSLC22A1rs594709 andSLC47A1rs2289669 polymorphisms were determined in 267 T2DM patients and 182 healthy subjects. Subsequently, 53 newly diagnosed patients who received metformin monotherapy were recruited to evaluate metformin efficacy.Results. No significant difference was found between T2DM patients and healthy subjects inSLC22A1rs594709 andSLC47A1rs2289669 allele frequencies and genotype frequencies. After metformin treatment,SLC22A1rs594709 GG genotype patients showed a higher increase in FINS (p=0.015) and decrease in HOMA-IS (p=0.001) and QUICKI (p=0.002) than A allele carriers.SLC47A1rs2289669 GG genotype patients had a higher decrease in TChol (p=0.030) and LDL-C (p=0.049) than A allele carriers. AmongSLC22A1rs594709 AA genotype, patients withSLC47A1rs2289669 AA genotype showed a higher decrease in FBG (p=0.015), PINS (p=0.041), and HOMA-IR (p=0.014) than G allele carriers. However, amongSLC22A1rs594709 G allele carriers,SLC47A1rs2289669 AA genotype patients showed a higher decrease in TChol (p=0.013) than G allele carriers.Conclusion. Our data suggest thatSLC22A1rs594709 andSLC47A1rs2289669 polymorphisms may influence metformin efficacy together in Chinese T2DM patients.

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The Association between Gene Polymorphism of TCF7L2 and Type 2 Diabetes in Chinese Han Population: A Meta-Analysis

PLoS ONE ◽

10.1371/journal.pone.0059495 ◽

2013 ◽

Vol 8 (3) ◽

pp. e59495 ◽

Cited By ~ 19

Author(s):

Haoying Dou ◽

Enting Ma ◽

Liqun Yin ◽

Yinghui Jin ◽

Hongwu Wang

Keyword(s):

Type 2 Diabetes ◽

Gene Polymorphism ◽

Meta Analysis ◽

Chinese Han Population ◽

Chinese Han ◽

Han Population

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Endothelial dysfunction and inflammatory biomarkers as a response factor of concurrent coenzyme Q10 add-on metformin in patients with type 2 diabetes mellitus

Journal of Laboratory Physicians ◽

10.4103/jlp.jlp_123_19 ◽

2019 ◽

Vol 11 (04) ◽

pp. 317-322

Author(s):

Hayder M. Al-Kuraishy ◽

Ali I. Al-Gareeb ◽

Hala A. Shams ◽

Farah Al-Mamorri

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Endothelial Dysfunction ◽

Coenzyme Q10 ◽

Healthy Subjects ◽

Model Assessment ◽

Inflammatory Changes

Abstract OBJECTIVES: The objective of the study was to evaluate the effect of metformin alone or in combination with coenzyme Q10 (CoQ10) on inflammatory changes and endothelial dysfunction in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: A total numbers of 54 patients with T2DM compared to 30 healthy subjects were divided into three groups: Group A (n = 30): healthy subjects without any medications; Group B (n = 24): T2DM patients treated with metformin 1 g/day; and Group C (n = 30): T2DM patients treated with metformin 1 g/day plus CoQ10, 300 mg/day. The duration of the study was 8 weeks. Fasting blood glucose, glycated hemoglobin, lipid profile, blood pressure variables, fasting insulin, insulin resistance, homeostatic model assessment of insulin resistance, vascular cell adhesion molecule 1 (VCAM-1), and E-selectin were measured before and after therapy. RESULTS: Metformin and/or CoQ10 therapy illustrated an insignificant effect on the fody mass index. This combination produced a significant improvement of metabolic changes in patients with T2DM (P < 0.01). sVCAM-1 serum level was decreased significantly after the initiation of metformin and/or CoQ10 therapy compared to the baseline P < 0.05. E-selectin was declined significantly following metformin monotherapy and after metformin plus CoQ10 therapy (P = 0.0001). CONCLUSION: CoQ10 add-on metformin therapy improves endothelial dysfunction and inflammatory changes in patients with T2DM alongside with amelioration of metabolic profile.

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Associations of Plasma BACE1 Level and BACE1 C786G Gene Polymorphism with Cognitive Functions in Patients with Type 2 Diabetes: A Cross- Sectional Study

Current Alzheimer Research ◽

10.2174/1567205017666200522210957 ◽

2020 ◽

Vol 17 (4) ◽

pp. 355-364 ◽

Cited By ~ 1

Author(s):

Sai Tian ◽

Rong Huang ◽

Dan Guo ◽

Hongyan Lin ◽

Jiaqi Wang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Gene Polymorphism ◽

Glycosylated Hemoglobin ◽

Fasting Blood Glucose ◽

Multivariable Logistic Regression Analysis ◽

Model Assessment ◽

Cross Sectional ◽

Logical Memory ◽

Bace1 Level

Background: β-Site APP-cleaving enzyme 1 (BACE1) is a key enzyme involved in the pathophysiology of Type 2 Diabetes Mellitus (T2DM) and Mild Cognitive Impairment (MCI). We aimed to investigate the potential associations of plasma BACE1 levels and BACE1 gene polymorphism with different cognitive performances in T2DM patients with MCI. Methods: The recruited 186 T2DM subjects were divided into 92 MCI group and 94 healthy-cognition controls, according to the Montreal Cognitive Assessment (MoCA) scores. Sociodemographic characteristics, clinical parameters and neuropsychological tests were assessed. BACE1 C786G gene polymorphism and plasma BACE1 level were determined. Results: Compared to controls, MCI patients exhibited higher plasma BACE1 levels. Plasma BACE1 levels were negatively associated with MoCA, Clock Drawing Test and Logical Memory Test scores, whereas positively associated with Trail Making Test-B time in the MCI group (all p<0.05), after adjusting fasting blood glucose, glycosylated hemoglobin, and homeostasis model assessment of insulin resistance by C-peptide. Multivariable logistic regression analysis showed a significant trend towards increased MCI risk with high plasma BACE1 level in T2DM patients (OR = 1.492, p = 0.027). The plasma BACE1 levels of GG and GC genotypes were obviously higher than that of CC genotype in T2DM-MCI patients (p = 0.035; p = 0.026, respectively). Conclusion: Increased plasma BACE1 levels were associated with poor overall cognition functions, especially visuospatial abilities, visual/logical memory and executive functions in T2DM-MCI patients. Additionally, elevated plasma BACE1 level was a risk factor for MCI in T2DM patients, and might be influenced by BACE1 C786G gene mutations.

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