Methylenetetrahydrofolate reductase gene polymorphism in diabetes and obesity.

Endocrinology and Metabolism Research Centre, Tehran University of Medical Sciences, Tehran, Iran.
Molecular Biology Reports (Impact Factor: 1.96). 05/2009; 37(1):105-9. DOI: 10.1007/s11033-009-9545-z
Source: PubMed

ABSTRACT Methylenetetrahydrofolate reductase (MTHFR) polymorphism may play an important role in the pathophysiology of obesity and diabetes accompanied by obesity due to its influence on plasma homocysteine levels. There are significant and sometimes very strong relationship between levels of homocysteine and several multi-system diseases including CHD and CVA. To examine the association between MTHFR gene C677T polymorphism in diabetes and obesity with serum homocysteine levels. A total of 682 subjects were recruited in four groups (Normal, obese, diabetic and obese and diabetics). MTHFR gene C677T polymorphism was detected using PCR-RFLP technique. Serum homocysteine levels were measured using HPLC. There was a significant increase in the mean serum homocysteine levels in subjects carrying TT genotype (34.6 +/- 26.5) compared to subjects carrying CC (15.1 +/- 8) or CT genotype (16.4 +/- 7.8) (P < 0.000). We found no significant differences for MTHFR allele and genotype frequencies between different groups. Our data have confirmed the association between serum homocysteine levels and MTHFR C677T genotype reported in other populations.

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Available from: Mahsa M Amoli, Jul 30, 2015
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    • "By contrast, isoforms of the methylenetetrahydrofolate reductase (MTHFR) enzyme have been implicated in diverse phenotypes. The MTHFR 677 C- T mutation [4] that results in a thermolabile enzyme and the MTHFR 1298 A-C mutation [5] have been associated with phenotypes ranging from coronary artery disease [6] to miscarriage [10] to diabetes and obesity [11] [12]. "
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    ABSTRACT: We evaluated single nucleotide polymorphism (SNP) detection via a target-capture, C-probe ligation, and RAM assay in a single-blind comparison to clinical samples that had been tested with FDA-cleared tests for up to 4 different vascular disease-related SNPs. In the RAM assay circulizable linear probes (C- or padlock probes) were annealed directly to genomic DNA, processed on a largely automated platform, and ligated C-probes were amplified by real-time RAM. After allele determinations were made with the experimental system, the sample genotypes were unblinded and the experimentally determined genotypes were found to be completely consistent with the FDA-cleared test results. The methods and results presented here show that a combination of C-probes, automated sample processing, and isothermal RAM provides a robust, and specific, nucleic acid detection platform that is compatible with automated DNA sample preparation and the throughput requirements of the clinical laboratory.
    03/2014; 2014:641090. DOI:10.1155/2014/641090
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    • "Previous studies suggested contribution of variants in homocysteine metabolism pathway genes in susceptibility to obesity, type 2 diabetes, or related traits [17] [18] [19]. Methylene tetrahydrofolate reductase (MTHFR) is shown to act synergistically with angiotensin-I-converting enzyme (ACE) to modulate type 2 diabetes risk [17]. "
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    ABSTRACT: Hyperhomocysteinemia, a risk factor for cardiovascular disorder, obesity, and type 2 diabetes, is prevalent among Indians who are at high risk of these metabolic disorders. We evaluated association of common variants of genes involved in homocysteine metabolism or its levels with type 2 diabetes, obesity, and related traits in North Indians. We genotyped 90 variants in initial phase (2.115 subjects) and replicated top signals in an independent sample set (2.085 subjects). The variant MTHFR-rs1801133 was the top signal for association with type 2 diabetes (OR = 0.78 (95%  CI = 0.67-0.92), P = 0.003) and was also associated with 2 h postload plasma glucose (P = 0.04), high-density lipoprotein cholesterol (P = 0.004), and total cholesterol (P = 0.01) in control subjects. These associations were neither replicated nor significant after meta-analysis. Studies involving a larger study population and different ethnic groups are required before ruling out the role of these important candidate genes in type 2 diabetes, obesity, and related traits.
    Experimental Diabetes Research 01/2012; 2012:960318. DOI:10.1155/2012/960318 · 3.54 Impact Factor
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    ABSTRACT: Hyperhomocysteinemia is regarded as a risk factor for cardiovascular diseases, diabetes and obesity. Manifestation of these chronic metabolic disorders starts in early life marked by increase in body mass index (BMI). We hypothesized that perturbations in homocysteine metabolism in early life could be a link between childhood obesity and adult metabolic disorders. Thus here we investigated association of common variants from homocysteine metabolism pathway genes with obesity in 3,168 urban Indian children. We genotyped 90 common variants from 18 genes in 1,325 children comprising of 862 normal-weight (NW) and 463 over-weight/obese (OW/OB) children in stage 1. The top signal obtained was replicated in an independent sample set of 1843 children (1,399 NW and 444 OW/OB) in stage 2. Stage 1 association analysis revealed association between seven variants and childhood obesity at P<0.05, but association of only rs2796749 in AMD1 [OR = 1.41, P = 1.5×10(-4)] remained significant after multiple testing correction. Association of rs2796749 with childhood obesity was validated in stage 2 [OR = 1.28, P = 4.2×10(-3)] and meta-analysis [OR = 1.35, P = 1.9×10(-6)]. AMD1 variant rs2796749 was also associated with quantitative measures of adiposity and plasma leptin levels that was also replicated and corroborated in combined analysis. Our study provides first evidence for the association of AMD1 variant with obesity and plasma leptin levels in children. Further studies to confirm this association, its functional significance and mechanism of action need to be undertaken.
    PLoS ONE 04/2012; 7(4):e33162. DOI:10.1371/journal.pone.0033162 · 3.53 Impact Factor
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