Dataset Information

Role of metabolizing MTHFR gene polymorphism (rs1801133) and its mRNA expression among Type 2 Diabetes.

ABSTRACT:

Objective

Type 2 Diabetes is a glucose metabolic disorder occurred by insulin insensitivity in which folate metabolism plays an important role. it is believed that polymorphism of Methylenetetrahydrofolate reductase (MTHFR) C677T linked with type 2 diabetes mellitus. However, results are conflicted. therefore, in this study we re-examine the relationship between MTHFR C677T in type 2 diabetes mellitus patients.

Methods

Present research work included 100 newly diagnosed type 2 diabetic mellitus (T2DM) cases and 100 healthy individuals. After the blood sample collection all the biochemical parameters were evaluated among the T2DM cases and healthy individuals. DNA and RNA extraction from whole blood was done to study the MTHFR gene polymorphism by allele specific polymerase chain reaction method and its expression analysis was done by quantitative real time polymerase chain reaction method.

Results

The significant difference was observed in genotype distribution among case and control group (p=0.0002). Compared with wildtype CC genotype, CT heterozygous (OR=2.95, 95% Cl=1.62-5.38) and TT homozygous (OR=3.20, CI=1.79-5.73) suggest to have effect of MTHFR polymorphism on type 2 mellitus risk. Moreover, relative MTHFR mRNA expression was found for wild type CC genotype 3.02-fold, CT heterozygous genotype 2.57 fold and mutant TT homozygous genotype 0.50-fold which is down regulated (p<0.0001).

Conclusion

Our results indicates that the polymorphism in MTHFR C677T plays significant role in type II diabetes risk. MTHFR CT heterozygous and mutant TT genotype showed reduced mRNA expression among the T2DM patients. However, large scale case-control studies are needed to strengthen such conclusion in the future.

SUBMITTER: Pathak D

PROVIDER: S-EPMC9167251 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Role of metabolizing MTHFR gene polymorphism (rs1801133) and its mRNA expression among Type 2 Diabetes.

Pathak Divya D Shrivastav Dharmsheel D Verma Amit K AK Alsayegh Abdulrahman A AA Yadav Prasant P Khan Nawaid Hussain NH Al-Harbi Alhanouf I AI Khan Mohammad Idreesh MI Bihade Kapil K Singh Desh Deepak DD Beg Mirza Masroor Ali MMA

Journal of diabetes and metabolic disorders 20220219 1

<h4>Objective</h4>Type 2 Diabetes is a glucose metabolic disorder occurred by insulin insensitivity in which folate metabolism plays an important role. it is believed that polymorphism of Methylenetetrahydrofolate reductase (MTHFR) C677T linked with type 2 diabetes mellitus. However, results are conflicted. therefore, in this study we re-examine the relationship between MTHFR C677T in type 2 diabetes mellitus patients.<h4>Methods</h4>Present research work included 100 newly diagnosed type 2 diab ...[more]

PMID: 35673506

Similar Datasets

Project description:BackgroundType 2 diabetes mellitus (T2DM) is a common complex metabolic disorder that exhibits a strong genetic predisposition. 5,10-methylenetetrahydrofolate reductase (MTHFR) regulates folate metabolism, which has been proposed to be associated with T2DM, although the relationship is inconsistent among different geographical areas. This study aimed to investigate the effects of MTHFR C677T (rs1801133) and A1298C (rs1801131) loci polymorphisms on T2DM susceptibility in the population of the Dali area in Yunnan Province, China.MethodsThis case-control study included 445 patients with T2DM and 272 healthy control individuals from the Dali area of Yunnan Province. Genotyping of the MTHFR gene polymorphisms was performed using the competitive allele-specific PCR (KASP) method. The effects of genetic variations of the MTHFR gene on T2DM risk were evaluated using odds ratios (OR) and 95% confidence intervals.ResultsThe results of the present study revealed that the TT genotype (OR = 1.750, P = 0.030) and the T allele (OR = 1.252, P = 0.047) at the MTHFR C677T locus were considerably associated with the increased odds of developing T2DM. In addition, the CC genotype (OR = 3.132, P = 0.032) at the MTHFR A1298C locus also substantially increased the odds of developing T2DM. The T-A haplotype (OR = 1.305, P = 0.030) of MTHFR C677T and A1298C exhibited the increased odds of developing T2DM. Biochemical index analyses showed that patients with T2DM who carried the CT or TT genotype of MTHFR C677T expressed substantially higher levels of fasting blood glucose (FBG), homocysteine (Hcy), and tumor necrosis factor-alpha (TNF-α) than those of the CC genotype. Moreover, the FBG and Hcy levels were considerably higher in patients with T2DM who carried the CC or AC genotype of MTHFR A1298C than those of the AA genotype. No obvious association was observed between these MTHFR polymorphisms and cardiovascular risk in T2DM.ConclusionOur study suggests that the genetic variations of MTHFR C677T and A1298C are significantly associated with T2DM susceptibility in the population of the Dali area of Yunnan Province, China.

Project description:BackgroundThe aetio-pathologenesis of hypertension is multifactorial, encompassing genetic, epigenetic, and environmental factors. The combined effect of genetic and epigenetic changes on hypertension is not known. We evaluated the independent and interactive association of MTHFR rs1801133 single nucleotide polymorphism (SNP) and MTHFR promoter methylation with hypertension among Taiwanese adults.MethodsWe retrieved data including, MTHFR promoter methylation, MTHFR rs1801133 genotypes (CC, CT, and TT), basic demography, personal lifestyle habits, and disease history of 1,238 individuals from the Taiwan Biobank (TWB).ResultsThe distributions of hypertension and MTHFR promoter methylation quartiles (β < 0.1338, 0.1338 ≤ β < 0.1385, 0.1385 ≤ β < 0.1423, and β ≥ 0.1423 corresponding to <Q1, Q1-Q2, Q2-Q3, and ≥Q3) among individuals with the rs1801133 genotypes (CC, CT, and TT) were significantly different (P < 0.05). The risk of hypertension was significantly higher among individuals with the TT genotype compared to the reference genotype (CC): odds ratio (OR); 95% confidence interval (CI) = 2.718; 1.503-4.914. The trend of the association of the CT and TT genotypes with hypertension was dose-dependent (P-trend = 0.0041). MTHFR promoter methylation (lower quartiles compared to ≥Q3) was not significantly associated with hypertension. However, its interaction with MTHFR rs1801133 was significant (P = 0.0323). After stratification by rs1801133 genotypes, lower MTHFR promoter methylation quartiles (<Q1, Q1-Q2, Q2-Q3) compared to ≥Q3 were significantly associated with a higher risk of hypertension among individuals carrying the CC genotype: ORs (95% CIs) = 3.225 (1.140-9.124), 4.177 (1.424-12.247), and 8.645 (2.513-29.739) for Q2-Q3, Q1-Q2, and <Q1, respectively. The trend test was significant (P-trend = 0.0009).ConclusionIndependently, rs1801133 TT was associated with a higher risk of hypertension, but methylation was not. Based on genotypes, lower methylation was dose-dependently associated with a higher risk of hypertension in individuals with the CC genotype. Our findings suggest that MTHFR rs1801133 and MTHFR promoter methylation could jointly influence hypertension susceptibility.

Project description:BackgroundThe 677C>T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene is considered to have a significant effect on colorectal cancer susceptibility, but the results are inconsistent. In order to investigate the association between the MTHFR 677C>T polymorphism and the risk of colorectal cancer, a meta-analysis was held based on 71 published studies.MethodsEligible studies were identified through searching the MEDLINE, EMBASE, PubMed, Web of Science, Chinese Biomedical Literature database (CBM) and CNKI database. Odds ratios (OR) and 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with x(2)-based Q-test. Begg's and Egger's test were also carried out to evaluate publication bias. Sensitive and subgroup analysis were also held in this meta-analysis.ResultsOverall, 71 publications including 31,572 cases and 44,066 controls were identified. The MTHFR 677 C>T variant genotypes are significantly associated with increased risk of colorectal cancer. In the stratified analysis by ethnicity, significantly increased risks were also found among Caucasians for CC vs TT (OR=1.076; 95%CI= 1.008-1.150; I(2) =52.3%), CT vs TT (OR=1.102; 95%CI=1.032-1.177; I(2) =51.4%) and dominant model (OR=1.086; 95%CI=1.021-1.156; I(2) =53.6%). Asians for CC vs TT (OR =1.226; 95%CI =1.116-1.346; I(2) =55.3%), CT vs TT (OR =1.180; 95%CI =1.079-1.291; I(2) =36.2%), recessive (OR =1.069; 95%CI =1.003-1.140; I(2) =30.9%) and dominant model (OR =1.198; 95%CI =1.101-1.303; I(2) =52.4%), and Mixed populations for CT vs TT (OR =1.142; 95%CI =1.005-1.296; I(2) =0.0%). However, no associations were found in Africans for all genetic models.ConclusionThis meta-analysis suggests that the MTHFR 677C>T polymorphism increases the risk for developing colorectal cancer, while there is no association among Africans found in subgroup analysis by ethnicity.

Dataset Information

Role of metabolizing MTHFR gene polymorphism (rs1801133) and its mRNA expression among Type 2 Diabetes.

Objective

Methods

Results

Conclusion

Publications

Role of metabolizing MTHFR gene polymorphism (rs1801133) and its mRNA expression among Type 2 Diabetes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets