Frequency distribution of the methylenetetrahydrofolate reductase polymorphisms in sickle cell hemoglobinopathy-A hospital based study in central India

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

doi:10.1016/j.cegh.2020.11.002

Cited by 3 publications

(3 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The frequency percentages of the homozygous variant genotypes CC1298 and TT677 were 25% and 8.06%, respectively, corroborated with the previously reported frequency of 19.7% and 2%, respectively, by Patel et al's study in this area [ 4 ]. Angeline et al recorded frequencies of 15.3% for CC1298 and 1.38% for TT677, and the MAF were 38.9% and 10.4%, respectively [ 16 ].…”

Section: Discussionsupporting

confidence: 90%

“…The respective MAFs recorded in the present study were 42.5% and 22.5%. The mutant allele percentage distribution among various regions in India varied nearly from 2% to 24% for T677 and 19% to 44% for C1298 [ 1 , 4 ]. The frequency distribution difference might reflect the distribution pattern in different geographical regions [ 17 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…The common single nucleotide polymorphisms (SNPs) observed are C677T (cytosine by thymine at position 677 of MTHFR gene, valine replaces alanine at position 222 of MTHFR protein) and A1298C (adenine by cytosine at position 1298 of MTHFR gene, glutamic acid to alanine at position 429 of MTHFR protein) [ 3 ]. The frequency of these variants in the Indian population is not uncommon and is reported to vary from nearly 2% to 24% for 677T and 19% to 44% for 298C [ 1 , 4 ]. The variant form of the enzymes demonstrates reduced activity [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Panigrahi¹,

Patel²,

Rajbhar³

et al. 2023

Cureus

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Panigrahi¹,

Patel²,

Rajbhar³

et al. 2023

Cureus

Self Cite

View full text Add to dashboard Cite

show abstract

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

et al. 2021

View full text Add to dashboard Cite

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 the genotypes accorded significant association with homocysteinemia (p < 0.001). Vascular crisis (p = 0.04), frequency of hospitalization (p < 0.001) and severity score (p = 0.02) revealed association with C677T and not with A1298C. The CT/TT677 genotypes showed 3.39-times (p = 0.032) to have higher score for severity. Conclusion: C677T depicted significant association with clinical severity in study population.

show abstract

Predictive Effect of Methylene Tetrahydrofolate Reductase Variants on Vascular Related Crisis

Patel,

Nanda,

Hussain

et al. 2023

Journal of Applied Hematology

View full text Add to dashboard Cite

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.

show abstract

Frequency distribution of the methylenetetrahydrofolate reductase polymorphisms in sickle cell hemoglobinopathy-A hospital based study in central India

Cited by 3 publications

References 20 publications

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

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

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

Predictive Effect of Methylene Tetrahydrofolate Reductase Variants on Vascular Related Crisis

Contact Info

Product

Resources

About