Association Between Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphisms and Susceptibility to Childhood Acute Lymphoblastic Leukemia in an Iranian Population

Overview

Journal Int J Hematol Oncol Stem Cell Res

Specialty Hematology

Date 2016 Aug 5

PMID 27489588

Citations 8

Authors

Gholamreza Bahari

Mohammad Hashemi

Majid Naderi

Mohsen Taheri

Affiliations

Soon will be listed here.

Abstract

Background: The present study was aimed to examine the possible association between methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms and childhood acute lymphoblastic leukemia (ALL) in a sample of Iranian population.

Subjects And Methods: A total of 220 subjects including 100 children diagnosed with ALL and 120 healthy children participated in the case-control study. The single nucleotide polymorphisms (SNPs) of MTHFR were determined by ARMS-PCR or PCR-RFLP method.

Results: Our investigation revealed that rs13306561 both TC and TC + CC genotypes decreased the risk of ALL compared to TT genotype (OR=0.32, 95%CI=0.15-0.68, p=0.002 and OR=0.35, 95%CI=0.17-0.70, p=0.003, respectively). In addition, the rs13306561 C allele decreased the risk of ALL in comparison with T allele (OR=0.42, 95% CI=0.22-0.78, P=0.005). MTHFR rs1801131 (A1298C) polymorphism showed that the AC heterozygous genotype decreased the risk of ALL in comparison with AA homozygous genotype (OR=0.43, 95%CI=0.21-0.90, p=0.037). Neither the overall Chi-square comparison of cases and control subjects (????2=5.54, p=0.063) nor the logistic regression analysis showed significant association between C677T polymorphism and ALL (OR=1.25, 95% CI=0.69-2.23, p=0.552; CT vs. CC).

Conclusion: The current investigation findings showed that MTHFR rs1801131 and rs13306561 polymorphisms decreased the risk of ALL in the population which has been studied. Further studies with larger sample sizes and different ethnicities are required to validate our findings.

Citing Articles

Gene Polymorphisms and Cancer Risk in Children and Adolescents: A Systematic Review and Meta-Analysis.

Kolanis S, Kotanidou E, Tsinopoulou V, Georgiou E, Hatzipantelis E, Fidani L Children (Basel). 2025; 12(1).

PMID: 39857939 PMC: 11764102. DOI: 10.3390/children12010108.

Cerebral sinuses thrombosis prior to the diagnosis of acute lymphoblastic leukemia in a child: A case report.

Sherief L, Zakaria M, Soliman B, Kamal N, Alharthi S, Abosabie S SAGE Open Med Case Rep. 2022; 10:2050313X221117337.

PMID: 35991951 PMC: 9382063. DOI: 10.1177/2050313X221117337.

The protective effects of the methylenetetrahydrofolate reductase rs1801131 variant among Saudi smokers.

Almutairi M, Al-Numair N, Reddy Parine N, Almutairi B, Alrefaei A, Rouabhia M Saudi J Biol Sci. 2021; 28(7):3972-3980.

PMID: 34220254 PMC: 8241599. DOI: 10.1016/j.sjbs.2021.04.011.

Genetics of blood malignancies among Iranian population: an overview.

Ghayour-Mobarhan M, Zangouei A, Hosseinirad S, Mojarrad M, Moghbeli M Diagn Pathol. 2020; 15(1):44.

PMID: 32375828 PMC: 7201799. DOI: 10.1186/s13000-020-00968-2.

Deregulation of folate pathway gene expression correlates with poor prognosis in acute leukemia.

Organista-Nava J, Gomez-Gomez Y, Del Moral-Hernandez O, Illades-Aguiar B, Gomez-Santamaria J, Rivera-Ramirez A Oncol Lett. 2019; 18(3):3115-3127.

PMID: 31452789 PMC: 6704278. DOI: 10.3892/ol.2019.10650.

References

Roy Moulik N, Parveen F, Kumar A, Awasthi S, Agrawal S . MTHFR gene polymorphism in acute lymphoblastic leukemia among North Indian children: a case-control study and meta-analysis updated from 2011. J Hum Genet. 2014; 59(7):397-404. DOI: 10.1038/jhg.2014.44. View

Sole X, Guino E, Valls J, Iniesta R, Moreno V . SNPStats: a web tool for the analysis of association studies. Bioinformatics. 2006; 22(15):1928-9. DOI: 10.1093/bioinformatics/btl268. View

Silva R, Fontes A, Silva K, SantAna T, Ramos F, Marques-Salles T . Polymorphisms involved in folate metabolism pathways and the risk of the development of childhood acute leukemia. Genet Test Mol Biomarkers. 2013; 17(2):147-52. DOI: 10.1089/gtmb.2012.0174. View

Ojha R, Gurney J . Methylenetetrahydrofolate reductase C677T and overall survival in pediatric acute lymphoblastic leukemia: a systematic review. Leuk Lymphoma. 2013; 55(1):67-73. DOI: 10.3109/10428194.2013.792336. View

Azhar M, Rahimi Z, Vaisi-Raygani A, Akramipour R, Madani H, Rahimi Z . Lack of association between MTHFR C677T and A1298C polymorphisms and risk of childhood acute lymphoblastic leukemia in the Kurdish population from Western Iran. Genet Test Mol Biomarkers. 2011; 16(3):198-202. DOI: 10.1089/gtmb.2011.0041. View

van der Put N, Gabreels F, STEVENS E, Smeitink J, Trijbels F, Eskes T . A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?. Am J Hum Genet. 1998; 62(5):1044-51. PMC: 1377082. DOI: 10.1086/301825. View

Bellampalli R, Phani N, Bhat K, Prasad K, Bhaskaranand N, Guruprasad K . Significance of 5,10-methylenetetrahydrofolate reductase gene variants in acute lymphoblastic leukemia in Indian population: an experimental, computational and meta-analysis. Leuk Lymphoma. 2014; 56(5):1450-9. DOI: 10.3109/10428194.2014.953154. View

Jiang Y, Hou J, Zhang Q, Jia S, Wang B, Zhang J . The MTHFR C677T polymorphism and risk of acute lymphoblastic leukemia: an updated meta-analysis based on 37 case-control studies. Asian Pac J Cancer Prev. 2014; 14(11):6357-62. DOI: 10.7314/apjcp.2013.14.11.6357. View

Schnakenberg E, Mehles A, Cario G, Rehe K, Seidemann K, Schlegelberger B . Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and susceptibility to pediatric acute lymphoblastic leukemia in a German study population. BMC Med Genet. 2005; 6:23. PMC: 1164414. DOI: 10.1186/1471-2350-6-23. View

10.

Li X, Liao Q, Zhang S, Chen M . Association of methylenetetrahytrofolate reductase (MTHFR) C677T and A1298C polymorphisms with the susceptibility of childhood acute lymphoblastic leukaemia (ALL) in Chinese population. Eur J Med Res. 2014; 19:5. PMC: 3932997. DOI: 10.1186/2047-783X-19-5. View

11.

Hashemi M, Hanafi Bojd H, Eskandari Nasab E, Bahari A, Hashemzehi N, Shafieipour S . Association of Adiponectin rs1501299 and rs266729 Gene Polymorphisms With Nonalcoholic Fatty Liver Disease. Hepat Mon. 2013; 13(5):e9527. PMC: 3734897. DOI: 10.5812/hepatmon.9527. View

12.

Ma Y, Sui Y, Wang L, Li H . Effect of GSTM1 null genotype on risk of childhood acute leukemia: a meta-analysis. Tumour Biol. 2013; 35(1):397-402. DOI: 10.1007/s13277-013-1055-x. View

13.

Sazawal S, Chaubey R, Kaur P, Chikkara S, Kumar B, Bakshi S . MTHFR Gene Polymorphisms and the Risk of Acute Lymphoblastic Leukemia in Adults and Children: A Case Control Study in India. Indian J Hematol Blood Transfus. 2014; 30(4):219-25. PMC: 4243392. DOI: 10.1007/s12288-013-0295-7. View

14.

Sohn K, Jang H, Campan M, Weisenberger D, Dickhout J, Wang Y . The methylenetetrahydrofolate reductase C677T mutation induces cell-specific changes in genomic DNA methylation and uracil misincorporation: a possible molecular basis for the site-specific cancer risk modification. Int J Cancer. 2009; 124(9):1999-2005. PMC: 2692263. DOI: 10.1002/ijc.24003. View

15.

Hashemi M, Sheybani-Nasab M, Naderi M, Roodbari F, Taheri M . Association of functional polymorphism at the miR-502-binding site in the 3' untranslated region of the SETD8 gene with risk of childhood acute lymphoblastic leukemia, a preliminary report. Tumour Biol. 2014; 35(10):10375-9. DOI: 10.1007/s13277-014-2359-1. View

16.

Wiemels J, Smith R, Taylor G, Eden O, Alexander F, Greaves M . Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia. Proc Natl Acad Sci U S A. 2001; 98(7):4004-9. PMC: 31169. DOI: 10.1073/pnas.061408298. View

17.

Frosst P, Blom H, Milos R, Goyette P, Sheppard C, Matthews R . A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995; 10(1):111-3. DOI: 10.1038/ng0595-111. View

18.

Balta G, Yuksek N, Ozyurek E, Ertem U, Hicsonmez G, Altay C . Characterization of MTHFR, GSTM1, GSTT1, GSTP1, and CYP1A1 genotypes in childhood acute leukemia. Am J Hematol. 2003; 73(3):154-60. DOI: 10.1002/ajh.10339. View

19.

Kim N, Chong S, Jang M, Ho Hong S, Kim H, Cho E . Association of the methylenetetrahydrofolate reductase polymorphism in Korean patients with childhood acute lymphoblastic leukemia. Anticancer Res. 2006; 26(4B):2879-81. View

20.

Zintzaras E, Doxani C, Rodopoulou P, Bakalos G, Ziogas D, Ziakas P . Variants of the MTHFR gene and susceptibility to acute lymphoblastic leukemia in children: a synthesis of genetic association studies. Cancer Epidemiol. 2011; 36(2):169-76. DOI: 10.1016/j.canep.2011.10.002. View