Relationship between MTHFR C677T and A1298C gene polymorphisms and complications of type 2 diabetes mellitus in an Emirati population

Chehadeh, Sarah W. El Hajj; Jelinek, Herbert F.; Mahmeed, Wael Al; Tay, Guan K.; Odama, Unini; ElGhazali, Gehad; Safar, Habiba S. Al

doi:10.1016/j.mgene.2016.04.002

Cited by 21 publications

(13 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The environmental factors we included in MDR were age, gender, BMI (body mass index), TG (triglyceride), TC (total cholesterol), LDL (low density lipoprotein), HDL (high density lipoprotein), FBG (fasting blood glucose), post-prandial blood glucose, HbA1c, duration of T2DM, patients with family history of diabetes, former smoking, current smoking, current smoking, current drinking, and patents with hypertension. SHEsis, an online software (http://analysis.bio-x.cn/myAnalysis.php), was used to identified the effects of haplotype frequencies on T2DM and its vascular complications (46–48).…”

Section: Methodsmentioning

confidence: 99%

Association of Polymorphisms in miRNA Processing Genes With Type 2 Diabetes Mellitus and Its Vascular Complications in a Southern Chinese Population

et al. 2019

View full text Add to dashboard Cite

Objective: To evaluate the potential association between the genetic variants in miRNA processing genes ( RAN, XPO5, DICER1 , and TARBP2 ) and susceptibility to type 2 diabetes mellitus (T2DM) and its vascular complications, as well as to further investigate their interaction with environmental factors in type 2 diabetes. Methods: We conducted a case-control study in genotyping of five polymorphic loci, including RAN rs14035, XPO5 rs11077, DICER1 rs13078, DICER1 rs3742330, and TARBP2 rs784567, in miRNA processing genes to explore the risk factors for T2DM and diabetic vascular complications. Haplotype analyses, interactions of gene-gene and interactions of gene-environment were performed too. Results: We identified a 36% decreased risk of developing T2DM in individuals with the minor A allele in DICER1 rs13078 (OR: 0.64; 95%CI: 0.42–0.95; P : 0.026). The AA haplotype in DICER1 was also associated with a protective effect on T2DM compared with the AT haplotype (OR: 0.63; 95%CI: 0.42–0.94; P -value: 0.023). T2DM patients with the TT+TC genotype at RAN rs14035 had a 1.89-fold higher risk of developing macrovascular complications than patients with the CC genotype (OR: 1.89; 95%CI: 1.04–3.45; P -value: 0.037). We also identified two three-factor interaction models. One is a three-factor [ DICER1 rs13078, body mass index (BMI), and triglyceride (TG)] interaction model for T2DM (OR: 5.93; 95%CI: 1.25–28.26; P = 0.025). Another three-factor [ RAN rs14035, hypertension (HP), and duration of T2DM (DOD)] interaction model was found for macrovascular complications of T2DM ( OR = 41.60, 95%CI = 11.75–147.35, P < 0.001). Conclusion: Our study provides new evidence that two single nucleotide polymorphisms (SNPs) of the miRNA processing genes, DICER1 and RAN , and their interactions with certain environmental factors might contribute to the risk of T2DM and its vascular complications in the southern Chinese population.

show abstract

Section: Methodsmentioning

confidence: 99%

Association of Polymorphisms in miRNA Processing Genes With Type 2 Diabetes Mellitus and Its Vascular Complications in a Southern Chinese Population

et al. 2019

View full text Add to dashboard Cite

show abstract

“…DR is the leading cause of blindness in adults [ 7 ]. Several studies point to the relationship between Hcy levels (hyperhomocysteinemia) and insulin resistance, which is the main cause of diabetic complications, such as DR and DN, in T2DM and cardiovascular diseases, especially when the polymorphism MTHFR C677T is present [ 8 , 9 ]. An elevation in plasma levels of Hcy results in an increase in oxidative stress inducing an increase in pro-inflammatory cytokines, endothelial dysfunction, DNA damage and hypomethylation [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Hypermethylation in the promoter of the MTHFR gene is associated with diabetic complications and biochemical indicators

Nunes

Silva

Evangelista

et al. 2017

Diabetol Metab Syndr

View full text Add to dashboard Cite

BackgroundDNA methylation is an epigenetic mechanism for regulating the transcription of many genes and has been linked to the development of various diseases. A promising gene to investigate is methylenetetrahydrofolate reductase (MTHFR), since the enzyme methylenetetrahydrofolate reductase (MTHFR) promotes methyl radical synthesis in the homocysteine cycle and can provide methyl groups for DNA methylation. In addition, several studies have correlated gene polymorphisms of this enzyme with a greater risk of diabetes, but little is known regarding the relationship between epigenetic changes in this gene and diabetes and its complications. The aim of this study was to investigate the relationship between methylation profile in the MTHFR gene promoter and biochemical, inflammatory and oxidative stress markers in individuals with type 2 diabetes (T2DM) who have been diagnosed for 5–10 years with or without diabetic retinopathy (DR) and nephropathy (DN).MethodsSpecific PCR for methylation (MSP) was used to analyze MTHFR methylation profile in leucocytes DNA. Biochemical markers (glycemia, glycated hemoglobin, total cholesterol, LDL, HDL, triglycerides, serum creatinine), inflammatory markers (C-reactive protein and alpha-1 acid glycoprotein) and oxidative stress (total antioxidant and malonaldehyde) were determined in peripheric blood samples and microalbuminuria in 24 h urine samples. The X2 and Mann–Whitney statistical tests were performed and p < 0.05 were considered significant.ResultsThe hypermethylated profile was most frequently observed in individuals with retinopathy (p < 0.01) and was associated with higher total cholesterol and LDL levels (p = 0.0046, 0.0267, respectively). Individuals with DN and hypermethylated profiles had higher levels of alpha-1 acid glycoprotein (p = 0.0080) and total antioxidant capacity (p = 0.0169) compared to subjects without complications.ConclusionsHypermethylation in the promoter of the MTHFR gene is associated with the occurrence of DR and with biochemical, inflammatory and oxidative stress parameters in the context of chronic complications

show abstract

“…Similarly, previous studies have found no significant associations between lipid/glucose metabolic indexes with MTHFR 1298 genotypes among T2DM patients [24,25]. Another study also has reported that BMI, hypertension, family history, HbA1c, total cholesterol, and fasting blood glucose of the diabetic patients segregated according to the MTHFR 1298 genotypes genotypes were similar except triglyceride levels [36].…”

Section: Association Of Mthfr 1298 Genotypes Versus Clinical and Biocmentioning

confidence: 51%

Association of MTHFR A1298c Gene Variant, Dna Damage, and Total Antioxidant Status With the Risk of Type 2 Diabetes Mellitus and Its Complications

Nithya

Isabel

Angeline

et al. 2018

Asian J Pharm Clin Res

View full text Add to dashboard Cite

Objectives:We have examined the association of methylenetetrahydrofolate reductase (MTHFR) gene A1298C variant, DNA damage, and total antioxidant status (TAS) in patients with type 2 diabetes mellitus (T2DM) with and without complications and in healthy controls.Methods: A total of 300 subjects including 100 patients with complications, 100 patients without complications, and 100 controls were included. TAS was assessed by ferric reducing ability of plasma assay. DNA damage was analyzed in lymphocytes using the comet assay. Polymerase chain reactionrestriction fragment length polymorphism analysis was performed to study the MTHFR A1298C gene polymorphism among the study subjects. Results:The results revealed that the MTHFR 1298 AC+CC genotypes were associated with increased risk (2 fold) for diabetes and its complications. When the effect of DNA damage was analyzed, significant differences between individuals with mutant and normal genotype among the diabetic patients (with and without complications) was observed (p≤0.001). In contrary, no significant difference was found between TAS and 1298 genotypes (AA versus AC+CC) in type 2 diabetic patients (with and without complications), p=0.338. We also found a significant difference between the genotypes of the MTHFR A1298C and DNA damage, TAS in T2DM patients (with and without complications) when compared to controls, p<0.001. Conclusions:Our findings suggest that the MTHFR A1298C gene polymorphism is considered as a risk factor for the development of diabetes and its complications among south Indians. Therefore, increased DNA damage and decreased TAS along with the occurrence of a mutant genotype in an individual with diabetes may be at an increased risk for the development of chronic complications.

show abstract

Relationship between MTHFR C677T and A1298C gene polymorphisms and complications of type 2 diabetes mellitus in an Emirati population

Cited by 21 publications

References 41 publications

Association of Polymorphisms in miRNA Processing Genes With Type 2 Diabetes Mellitus and Its Vascular Complications in a Southern Chinese Population

Association of Polymorphisms in miRNA Processing Genes With Type 2 Diabetes Mellitus and Its Vascular Complications in a Southern Chinese Population

Hypermethylation in the promoter of the MTHFR gene is associated with diabetic complications and biochemical indicators

Association of MTHFR A1298c Gene Variant, Dna Damage, and Total Antioxidant Status With the Risk of Type 2 Diabetes Mellitus and Its Complications

Contact Info

Product

Resources

About