Methylenetetrahydrofolate Reductase Polymorphisms As Genetic Markers to Predict Homocysteinemia and Clinical Severity in Sickle Cell Disease

Patel, Suprava; Nanda, Rachita; Hussain, Nighat; Mohapatra, Eli; Patra, Pradeep Kumar

doi:10.2217/bmm-2020-0613

Biomark. Med.

2021

DOI: 10.2217/bmm-2020-0613

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Methylenetetrahydrofolate Reductase Polymorphisms As Genetic Markers to Predict Homocysteinemia and Clinical Severity in Sickle Cell Disease

Suprava Patel

Rachita Nanda

Nighat Hussain

et al.

Abstract: Aim: The present study observed the relationship between the methylenetetrahydrofolate reductase genotypes and clinical outcome in children with sickle cell disorder. Methodology: A total of 249 children were recruited for the study and evaluated clinically for calculating severity score, homocysteine levels and C677T and A1298C genotyping. Results: The frequencies of variant genotypes were 28.1% CT/TT677 and 69.1% AC/CC1298. Plasma homocysteine was significantly elevated in variant groups (p < 0.001). Both… Show more

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2023

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Cited by 2 publications

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Predictive Effect of Methylene Tetrahydrofolate Reductase Variants on Vascular Related Crisis

Patel,

Nanda,

Hussain

et al. 2023

Journal of Applied Hematology

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BACKGROUND: Homocysteinemia is regarded as potential predictor for vaso-occlusive phenomenon often observed in sickle cell hemoglobinopathy. The objective was to determine the relationship of these genotypes with homocysteinemia and the predictive coefficient of these polymorphisms on the vascular-related crisis in the presence of sickle cell gene. MATERIALS AND METHODS: The case-control study comprised 89 children diagnosed with sickle disease with features of vascular crisis, 160 children without crisis and 252 apparently healthy children as the control group. The genotypes were assayed for C677T and A1298C variants and their association and predictor effect for homocysteinemia of different grades were analyzed. Sequential multiple regression model was used to assess the predictive effect. RESULTS: Homocysteine levels were significantly higher in the crisis group (P < 0.001). When compared to the wild genotype the variants depicted significantly raised homocysteine levels (P < 0.001). The prevalence of C677T was 29.9% and that for A1298 was 66.3% in the study population. The odds for crisis was 2.3 times for crisis in TT677 and 1.34 times in CC1298 variants. The genotypes revealed a significant association with different grades of homocysteinemia (P < 0.001). Plasma homocysteine depicted significant negative correlation with weight, height, body mass index and hemoglobin levels. None of the TT variants reported normal homocysteine values. Shift toward the variant form showed an increase of homocysteine levels by 7.3 units and 6.9 units for C677T and A1298C single-nucleotide polymorphisms respectively. CONCLUSION: Co-presence of methylenetetrahydrofolate reductase C677T and A1298C polymorphisms could be important predictor for homocysteinemia and thus contribute toward vascular crisis in sickle cell patients.

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Predictive Effect of Methylene Tetrahydrofolate Reductase Variants on Vascular Related Crisis

Patel,

Nanda,

Hussain

et al. 2023

Journal of Applied Hematology

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Association of Methylenetetrahydrofolate Reductase Gene Polymorphism in Mothers With Adverse Clinical Outcomes in Neonates

Panigrahi¹,

Patel²,

Rajbhar³

et al. 2023

Cureus

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Background: The presence of polymorphic methylenetetrahydrofolate reductase (MTHFR) in mothers poses a risk for numerous detrimental outcomes in neonates. The present study investigated the association of maternal MTHFR A1298C and C677T single nucleotide polymorphisms (SNPs) with the clinical outcomes in their neonates.Materials and methods: The cross-sectional study included 60 mothers and their neonates. Blood samples from mothers were analyzed for MTHFR A1298C and C677T SNP genotyping by real-time polymerase chain reaction. Clinical details of mothers and neonates were documented. Study groups were stratified based on wild, heterozygous, and mutant genotypes for the respective polymorphisms observed in mothers. Multinomial regression was applied for the association, followed by gene model formulation to estimate the impact of the genetic variants on the outcomes.Results: The frequency percentages of mutant CC1298 and TT677 genotypes were 25% and 8.06%, respectively, and the mutant allele frequencies (MAF) were 42.5% and 22.5%. Percentages of adverse outcomes such as intrauterine growth restriction, sepsis, anomalies, and mortality were higher in neonates born to mothers with homozygous mutant genotypes. Maternal C677T MTHFR SNPs revealed a significant association with neonatal anomalies (p = 0.001). The multiplicative risk model depicted OR (95% CI) for CT vs. CC+TT as 3.0 (95% CI: 0.66-13.7), and for TT vs. CT+CC was 15 (95% CI: 2.01-112.12). The C677T SNP in mothers predicted a dominant model for neonatal death (OR (95% CI): 5.84 (0.57-60.03), p = 0.15), whereas the A1298C reported recessive model for 1298CC mothers (OR (95% CI): 11 (1.05-115.5), p = 0.02). Both the genotypes assumed a recessive model for adverse neonatal outcomes: OR (95%CI) for CC vs. AA+AC was 3.2 (0.79-12.9, p = 0.1), and for TT vs. CC+CT was 5.48 (0.57-175.7, p = 0.2). The risk for sepsis in neonates was nearly six times higher in those born from mothers with homozygous CC1298 and TT677 than in the wild and heterozygous variants.Conclusion: Mothers with C677T and A1298C SNPs are highly susceptible to adverse outcomes in their neonates. Hence, screening the SNPs during the antenatal period can purposefully serve as a better predictive marker, following which proper clinical management could be planned.

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Methylenetetrahydrofolate Reductase Polymorphisms As Genetic Markers to Predict Homocysteinemia and Clinical Severity in Sickle Cell Disease

Cited by 2 publications

References 24 publications

Predictive Effect of Methylene Tetrahydrofolate Reductase Variants on Vascular Related Crisis

Predictive Effect of Methylene Tetrahydrofolate Reductase Variants on Vascular Related Crisis

Association of Methylenetetrahydrofolate Reductase Gene Polymorphism in Mothers With Adverse Clinical Outcomes in Neonates

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