Methylenetetrahydrofolate reductase gene polymorphisms and risk of acute lymphoblastic leukemia in children

Adiga, M. N. Sadananda; Chandy, Sunil Thomas; Ramachandra, Nallur B.; Appaji, L.; Kumari, Babita; Ramaswamy, Girija; Savithri, H.S.; Krishnamoorthy, Lakshmi

doi:10.4103/0019-509x.58858

Cited by 29 publications

(7 citation statements)

References 26 publications

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“…Six studies [23,25,28,39,44,46] involved adult ALL patients, 26 [5,24,26,27,30-35,37,38,40,42,43,45,47-54] involved pediatric patients and 3 [29,36,41] involved a mixed population of adult and childhood patients. The identified studies were undertaken in a wide range of ethnicities: 15 [23,27-33,37,38,43,45,47,52,54] providing data on Caucasians, 7 [35,36,39,44,46,48,49] on East Asians (Chinese and Korean), and 13 [5,24-26,33,34,40,42,43,48,50,51,53] on other ethnic origins. Twenty-one studies [5,26,28-31,33,38-41,43-45,49-54] involved general population-based controls and 5 studies [23,27,34,42,45] involved hospital-based controls, 9 studies [24,25,32,35-37,47,48] did not describe the source of their controls.…”

Section: Resultsmentioning

confidence: 99%

“…Twenty-one studies [5,26,28-31,33,38-41,43-45,49-54] involved general population-based controls and 5 studies [23,27,34,42,45] involved hospital-based controls, 9 studies [24,25,32,35-37,47,48] did not describe the source of their controls. Different genotyping methods were used: polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analysis was used in 26 studies [5,23,24,26,28,29,31,33,34,36-40,44-51,53,54], real-time PCR was used in 8 studies [25,31,32,41-44,52] and allele-specific oligonucleotide hybridization (ASO) was used in 2 studies [27,35]. In most studies, authors reported that the diagnosis of ALL was based on morphologic and immunophenotypic criteria.…”

Section: Resultsmentioning

confidence: 99%

“…In most studies, authors reported that the diagnosis of ALL was based on morphologic and immunophenotypic criteria. Eight studies [23,24,28,34,39,47,49,51] stated that the controls were age and gender matched. Only one study [23] mentioned genotyping was performed under blind conditions.…”

Section: Resultsmentioning

confidence: 99%

“…Only one study [23] mentioned genotyping was performed under blind conditions. Twelve studies provided data for combined genotype distribution of C677T and A1298C variants [23,27,31,32,34,35,38,42,46,50,51] and 4 studies provided analysis of haplotypes for these two variants [39,44,46,53]. In three studies [26,36,39] on C677T and two studies [38,50] on A1298C, the distribution of the genotypes in control group were found to deviate from HWE according to P value ( P < 0.05).…”

Section: Resultsmentioning

confidence: 99%

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Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Acute Lymphoblastic Leukemia-Evidence from an updated meta-analysis including 35 studies

Wang

Zhao

et al. 2012

BMC Med Genet

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Background5,10-methylenetetrahydrofolate reductase (MTHFR) variants, C677T and A1298C, have been reported to be associated with decreased risk of acute lymphoblastic leukemia (ALL). However, results derived from individually underpowered studies are conflicting. We carried out an updated meta-analysis on the association between MTHFR polymorphisms and ALL risk.MethodsRelevant publications were searched through PUBMED and EMBASE databases. The associations between MTHFR C677T and A1298C polymorphisms and the risk of ALL were evaluated by odds ratios (ORs). The heterogeneity and publication bias were estimated. Meta-regression analysis was performed to evaluate the potential sources of heterogeneity.ResultsC677T polymorphism was associated with a reduced risk of ALL (allele contrast: ORRE = 0.91, 95% CI: 0.83-0.99). Subgroup analysis showed MTHFR C677T variant was associated with decreased susceptibility to ALL in children and Caucasians. Meta-regression showed the logOR for the association between T allele and ALL increased as sex ratio (M/F) in the case group increased (P = 0.01). Regarding A1298C polymorphism, no significant association was observed (allele contrast: ORRE = 1.01, 95% CI: 0.91-1.11). There was no publication bias for C677T or A1298C polymorphism.ConclusionsThe present meta-analysis suggests that the C677T polymorphism, not A1298C, in MTHFR gene is associated with a decreased risk of ALL, particularly among children and Caucasians subjects. Our findings suggest that the influence of the C677T polymorphism on ALL susceptibility is modified by sex ratio in cases (M/F). Since folate intake may be a possible confounding factor, including this factor in future prospective studies is warranted. Further meta-analysis studies should be at least stratified for folate levels and gender to give more powerful and informative results.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Acute Lymphoblastic Leukemia-Evidence from an updated meta-analysis including 35 studies

Wang

Zhao

et al. 2012

BMC Med Genet

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“…Genotyping protocols were adjusted from those proposed by Sadananda Adiga et al [35] for MTHFR C677T and Hinks et al [27] for ATIC T675C.…”

Section: Methodsmentioning

confidence: 99%

Prediction of Methotrexate Clinical Response in Portuguese Rheumatoid Arthritis Patients: Implication ofMTHFRrs1801133 andATICrs4673993 Polymorphisms

Lima

Monteiro

Bernardes

et al. 2014

BioMed Research International

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Objective. Methotrexate (MTX), the most used drug in rheumatoid arthritis (RA) treatment, showing variability in clinical response, is often associated with genetic polymorphisms. This study aimed to elucidate the role of methylenetetrahydrofolate reductase (MTHFR) C677T and aminoimidazole carboxamide adenosine ribonucleotide transformylase (ATIC) T675C polymorphisms and clinicopathological variables in clinical response to MTX in Portuguese RA patients. Methods. Study included 233 RA patients treated with MTX for at least six months. MTHFR C677T and ATIC T675C polymorphisms were genotyped and clinicopathological variables were collected. Statistical analyses were performed and binary logistic regression method adjusted to possible confounding variables. Results. Multivariate analyses demonstrated that MTHFR 677TT (OR = 4.63; P = 0.013) and ATIC 675T carriers (OR = 5.16; P = 0.013) were associated with over 4-fold increased risk for nonresponse. For clinicopathological variables, noncurrent smokers (OR = 7.98; P = 0.001), patients positive to anti-cyclic citrullinated peptide (OR = 3.53; P = 0.004) and antinuclear antibodies (OR = 2.28; P = 0.045), with higher health assessment questionnaire score (OR = 2.42; P = 0.007), and nonsteroidal anti-inflammatory drug users (OR = 2.77; P = 0.018) were also associated with nonresponse. Contrarily, subcutaneous administration route (OR = 0.11; P < 0.001) was associated with response. Conclusion. Our study suggests that MTHFR C677T and ATIC T675C genotyping combined with clinicopathological data may help to identify patients whom will not benefit from MTX treatment and, therefore, assist clinicians in personalizing RA treatment.

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A meta‐analysis of MTHFR C677T and A1298C polymorphisms and risk of acute lymphoblastic leukemia in children

Yan

Yin

Dreyer

et al. 2011

Pediatric Blood & Cancer

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Methylenetetrahydrofolate reductase gene polymorphisms and risk of acute lymphoblastic leukemia in children

Abstract: The prevalence of 'T' allele for 677 MTHFR polymorphism was low in the population studied. There was no association between MTHFR 677 C-->T and 1298 A-->C gene polymorphisms and risk of ALL, which may be due to the small sample size.

Cited by 29 publications

References 26 publications

Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Acute Lymphoblastic Leukemia-Evidence from an updated meta-analysis including 35 studies

Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Acute Lymphoblastic Leukemia-Evidence from an updated meta-analysis including 35 studies

Prediction of Methotrexate Clinical Response in Portuguese Rheumatoid Arthritis Patients: Implication ofMTHFRrs1801133 andATICrs4673993 Polymorphisms

A meta‐analysis of MTHFR C677T and A1298C polymorphisms and risk of acute lymphoblastic leukemia in children

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