Peripheral neuropathy risk and a transcobalamin polymorphism: connecting the dots between excessive folate intake and disease susceptibility

Green, Ralph

doi:10.3945/ajcn.116.146365

Cited by 3 publications

(2 citation statements)

References 9 publications

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“…Third, metaanalyses that have assessed the association of rs1801198 with primary risk of pathologic conditions included geneticassociation studies with relatively low quality and, thus, should be interpreted with caution. Fourth, the present meta-analysis did not assess genetic association studies on rs1801198 according to folate status, and notably, those dealing with pathologic conditions (15). Future genetic association studies should address this issue.…”

Section: Discussionmentioning

confidence: 99%

“…We reported that this variant was a TCN2 polymorphism (rs1801198; NM_000355.2:c.776G.C; NP_000346.2:p.Arg259Pro) that influences the cellular expression and plasma concentration of TCN2 and the availability of cobalamin (13,14), thus suggesting that there is a potential influence of rs1801198 on the concentration of one-carbon metabolism (OCM) markers and primary risk of disease. Since the previous reports, several studies have assessed the association between the TCN2 rs1801198 and OCM marker concentrations or primary risk of disease such as congenital abnormalities or cancer with mixed results that have been reported, which may be explained by differences in the study design and power, genetic background of the studied populations, and nutritional status (15).…”

Section: Introductionmentioning

confidence: 99%

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Association of TCN2 rs1801198 c.776G>C polymorphism with markers of one-carbon metabolism and related diseases: a systematic review and meta-analysis of genetic association studies

Oussalah

Lévy

Filhine-Trésarrieu

et al. 2017

The American Journal of Clinical Nutrition

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Background: Vitamin B-12 (cobalamin) deficiency may produce severe neurologic and hematologic manifestations. Approximately 20-25% of circulating cobalamin binds to transcobalamin 2 (TCN2), which is referred to as active vitamin B-12. The G allele of the TCN2 c.776G.C (rs1801198) polymorphism has been associated with a lower plasma concentration of holotranscobalamin. However, genotype association studies on rs1801198 have led to conflicting results regarding its influence on one-carbon metabolism (OCM) markers or its association with pathologic conditions. Objective: We assessed the association of rs1801198 genotypes with OCM marker concentrations and primary risks of congenital abnormalities, cancer, and Alzheimer disease. Design: We conducted a systematic review of the literature that was published from January 1966 to February 2017 and included all studies that assessed the association between rs1801198 and OCM markers or a pathologic condition. Results: Thirty-four studies met the inclusion criteria. Subjects with the rs1801198 GG genotype had significantly lower concentrations of holotranscobalamin [standardized mean difference (SMD): 20.445 (95% CI: 20.673, 20.217; P , 0.001); I 2 = 48.16% (95% CI: 0.00%, 78.10%; P = 0.07)] and higher concentrations of homocysteine (European descent only) [SMD: 0.070 (95% CI: 0.020, 0.120; P = 0.01); I 2 = 0.00% (95% CI: 0.00%, 49.59%; P = 0.73)] than did subjects with the rs1801198 CC genotype. The meta-analysis on the association between rs1801198 and methylmalonic acid (MMA) lacked statistical power. No significant difference was observed regarding cobalamin, folate, and red blood cell folate. No significant association was observed between rs1801198 and primary risks of congenital abnormalities, cancer, or Alzheimer disease. Conclusions: Meta-analysis results indicate an influence of rs1801198 on holotranscobalamin and homocysteine concentrations in Europeandescent subjects. In addition, well-designed and -powered studies should be conducted for assessing the association between rs1801198 and MMA and clinical manifestations that are linked to a decreased availability of cobalamin. This review was registered at www.crd.york.ac.uk/prospero as CRD42017058504.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of TCN2 rs1801198 c.776G>C polymorphism with markers of one-carbon metabolism and related diseases: a systematic review and meta-analysis of genetic association studies

Oussalah

Lévy

Filhine-Trésarrieu

et al. 2017

The American Journal of Clinical Nutrition

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MTHFD1 c.1958G>A and TCN2 c.776G>C polymorphisms of folate metabolism genes and their implication for oral cavity cancer

Malinowska

Nowak-Zduńczyk

Merecz-Sadowska

et al. 2022

Postępy Higieny I Medycyny Doświadczalnej

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Background Cancers of the head and neck can damage the brain, spinal cord, and nerves, as well as the sense organs responsible for contact with the outside world. Oncogenic transformation occurs following mutations that change the function of specific genes, such tumor suppressor genes or oncogenes, and their encoded protein products. Therefore, the aim of this study was to evaluate the relationship between the occurrence of MTHFD1 c.1958G>A and TCN2 c.776G>C gene polymorphisms and the risk of oral cavity cancer. Materials and methods The study population consisted of 439 patients and 200 healthy subjects. Genomic DNA was extracted from peripheral blood and from paraffin-embedded tissue. Analysis of the gene polymorphisms was performed using polymerase chain reaction–restriction fragment length polymorphism. Results Statistically significant differences were found in the distribution of genotypes of the rs2236225 and rs1801198 polymorphisms between patients and controls. Regarding MTHFD1 c.1958G>A, the GA genotype (p<0.0001, OR = 2.91, 95% CI = 1.88–4.49-GA) was more common among patients than healthy subjects. Regarding TCN2 c.776G>C, the frequency of CC genotype (p< 0.0001, OR = 0.17, 95% CI = 0.10–0.33-CC) was significantly less common among patients than healthy subjects. Tobacco smoking, alcohol use, and male gender (p<0.0001) were found to be predictors of the disease. Conclusion The results suggest that the MTHFD1 c.1958G>A polymorphism may be associated with a greater risk of oral cavity cancer, whereas a protective effect has been found for the TCN2 c.776G>C polymorphism.

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Comparison of TCN-2 (776C>G) Gene Polymorphism and Vitamin B12 Status with Different Body Mass Index among Saudi Adults

Ashfaq

Aljaadi

Salaka

et al. 2023

Life

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Background: Overweight and obesity (OO) are significant public health issues, and many elements, including genetics, epigenetics, sedentary lifestyle, comorbid conditions, psychological and environmental pressures, have been linked to OO. More than 2 billion people are presently impacted by the global obesity epidemic, which is still advancing relentlessly. It is a significant public health concern and a major contributor to healthcare costs, because it increases the chance of developing conditions such as heart disease, stroke, type 2 diabetes, and chronic kidney disease (CKD). Using the ranges of 18.5–25 for normality, 25–30 for overweight, and 30 for obesity, BMI (in kg/m2) is used to identify obesity. Vitamin deficiency is one of the causative factors associated with the increasing trend of obesity. Altered vitamin B12 status is a multifactorial trait; changes in B12 status are produced by several single nucleotide polymorphisms (SNPs) in various genes that interact with the environment. They also support coordinated efforts to alter the built environment that is causing the obesity pandemic. Therefore, the present study aimed to evaluate the TCN-2 (776C>G) gene alteration and vitamin B12 levels with respect to different body mass index, as well as associating BMI with other biochemical parameters. Methods: 250 individuals were involved in the study; among them, 100 were in the healthy weight range category (BMI: 18.5 to <25 kg/m2), 100 were overweight (BMI: 25.0 to <30 kg/m2), and 50 were obese (BMI: >30 kg/m2). Participants visited during the screening program were subjected to blood pressure measurement, and further peripheral blood samples were drawn from all the participants in plain as well as in EDTA vials for biochemical (lipid profile and vitamin B12 level) analysis and single nucleotide polymorphism studies. Extracted DNA from whole blood collected in EDTA vials using kit protocol was used for genotyping by PCR-RFLP. Results: The levels of systolic (p < 0.0001) and diastolic blood pressures (p < 0.0001), HDL (p < 0.0001), LDL (p = 0.04), TG (p < 0.0001), cholesterol (p < 0.0001), and VLDL (p < 0.0001) showed significant differences between healthy controls, overweight, and obese groups. The healthy control TCN-2 (776C>G) genotypes were compared with those of overweight and obese participants, and compared to the healthy controls it was observed that overweight (p = 0.01) and obese (p = 0.002) subjects had significant differences in TCN-2 (776C>G) genotypes. For genotypes CG and GG, the odds ratio was 1.61 (0.87–2.95; p = 0.12), and 3.81 (1.47–9.88; p = 0.005) for overweight participants, respectively, and obese participants’ calculated odds ratios were 2.49 (1.16–5.36; p = 0.01) and 5.79 (1.93–17.35; p = 0.001), respectively. The relative risk for genotypes CG and GG, was 1.25 (0.93–1.68; p = 0.12), 2.17 (1.12–4.17; p = 0.02) for overweight participants, while the obese participants’ calculated relative risks were 1.31 (1.03–1.68; p = 0.01) and 2.02 (1.12–3.65; p = 0.001), respectively. Vitamin B12 levels were analyzed, and it was observed that a significant difference existed among overweight (305.5 pmol/L, p < 0.0001) and obese patients (229 pmol/L, p < 0.0001), respectively, as compared to healthy controls (385.5 pmol/L). Correlation analysis showed a significant association of vitamin B12 level with TG, cholesterol and VLDL; it showed a negative correlation, suggesting that decreases in B12 levels may impact the lipid profile. Conclusion: The study concluded that a predisposition to the GG genotype of TCN-2 gene polymorphism (776C>G) may increase susceptibility to obesity and the related complications, and higher odds and relative risk for the GG genotype may increase the risk of having obesity and further related complications. Lower vitamin B12 levels were linked with obesity and overweight, and impaired lipid parameters suggested that lower vitamin B12 may impact the altered lipid profile.

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Peripheral neuropathy risk and a transcobalamin polymorphism: connecting the dots between excessive folate intake and disease susceptibility

Cited by 3 publications

References 9 publications

Association of TCN2 rs1801198 c.776G>C polymorphism with markers of one-carbon metabolism and related diseases: a systematic review and meta-analysis of genetic association studies

Association of TCN2 rs1801198 c.776G>C polymorphism with markers of one-carbon metabolism and related diseases: a systematic review and meta-analysis of genetic association studies

MTHFD1 c.1958G>A and TCN2 c.776G>C polymorphisms of folate metabolism genes and their implication for oral cavity cancer

Comparison of TCN-2 (776C>G) Gene Polymorphism and Vitamin B12 Status with Different Body Mass Index among Saudi Adults

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