Association of a Polymorphism in the Gene Encoding Methylenetetrahydrofolate Dehydrogenase 1 (MTHFD1) 1958G>A with Orofacial Cleft
Keywords:Cleft Palate, Cleft Lip, Genetic Variation, Polymorphism, Genetic
Objective: To evaluate the possible association of a polymorphism in the gene encoding methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), 1958G>A, with the susceptibility to orofacial cleft in an Indonesian population. Material and Methods: A total of 200 stored secondary biological samples from 30 cases of orofacial cleft and 170 unaffected controls were analyzed to determine the polymorphism status at base 1958. The analysis was conducted using the PCR-restriction fragment length polymorphism technique after digestion with the Msp1 restriction enzyme. The samples were then subjected to agarose gel electrophoresis to investigate the presence or absence of the following fragments: genotype GG, 196, 86 and 40 base pairs (bp); genotype AA, 282 and 28 bp and genotype AG, 282, 196, 86, 40 and 28 bp. The test groups were compared using the Chi-square test. Results: The wild-type allele containing 1958G, as well as the genotype GG, were significantly more common in the control group than in the orofacial cleft group. Conclusion: The MTHFD1 1958G>A polymorphism was significantly associated with orofacial cleft susceptibility in the tested Indonesian population.
Allam E, Windsor LJ, Stone C, Allam E, Windsor L, Stone C. Cleft lip and palate: etiology, epidemiology, preventive and intervention strategies. Anat Physiol 2014; 4:150. https://doi.org/10.4172/2161-0940.1000150
KEMENKESRI. Riset kesehatan dasar. Jakarta: Badan Penelitian dan Pengembangan Kesehatan Departemen Kesehatan Republik Indonesia; 2013. p. 228. [In Indonesian].
Allagh KP, Shamanna BR, Murthy GV, Ness AR, Doyle P, Neogi SB, et al. Birth prevalence of neural tube defects and orofacial clefts in India: A systematic review and meta-analysis. Plos One 2015; 10(3):e0118961. https://doi.org/10.1371/journal.pone.0118961
Lesmana S, Auerkari EI. Genes contributing in cleft lip and cleft palate: A literature review. J Int Dent Med Res 2017; 9:441-8.
Neagos D, Cretu R, Tutulan-Cunita A, Stoian V, Bohiltea LC. Methylenetetrahydrofolate dehydrogenase (MTHFD) enzyme polymorphism as a maternal risk factor for trisomy 21: a clinical study. J Med Life 2010; 3(4):454-7.
Murthy J, Gurramkonda VB, Lakkakula BV. Significant association of MTHFD1 1958G>A single nucleotide polymorphism with nonsyndromic cleft lip and palate in Indian population. Med Oral Patol Oral Cir Bucal 2014; 19(6):e616-21. https://doi.org/10.4317/medoral.19796
Wehby GL, Murray JC. Folic acid and orofacial clefts: a review of the evidence. Oral Dis 2010; 16(1):11-9. https://doi.org/10.1111/j.1601-0825.2009.01587.x
Momb J, Lewandowski JP, Bryant JD, Fitch R, Surman DR, Vokes SA, et al. Deletion of Mthfd1l causes embryonic lethality and neural tube and craniofacial defects in mice. Proc Natl Acad Sci U S A 2013; 110(2):549-54. https://doi.org/10.1073/pnas.1211199110
Tania SF, Kim KR, Suhartono AW, Latief EI Auerkari. Distribution of E-cadherin 1 (CDH1) promoter methylation in patients with orofacial cleft. J Phys Conf Ser 2018; 1073(3):032064. https://doi.org/10.1088/1742-6596/1073/3/032064
Jessica C, Alwadris TT, Prasetyo SR, Puspitawati R, Auerkari EI. Association of interleukin 8-251 A/T gene polymorphism with periodontitis in Indonesia. J Phys: Conf Ser 2018;1025(1):012071. https://doi.org/10.1088/1742-6596/1025/1/012071
Auerkari EI, Suryandari DA, Umami SS, Kusdhany LS, Siregar TWA, Rahardjo TBW, Talbot C, Hogervorst E. Gene promoter polymorphism of RUNX2 and risk of osteoporosis in postmenopausal Indonesian women. SAGE Open Med 2014; 2:2050312114531571. https://doi.org/10.1177/2050312114531571
Wu J, Chen Y, Pei J, Pan J. MTHFD1 gene polymorphisms as risk factors involved in orofacial cleft: an independent case-control study and a meta-analysis. Int J Clin Exp Med 2015; 8(5):7737-45.
Mostowska A, Hozyasz KK, Jagodzinski PP. Maternal MTR genotype contributes to the risk of non-syndromic cleft lip and palate in the Polish population. Clin Genet 2006; 69(6): 512-7.
Boyles AL, Wilcox AJ, Taylor JA, Meyer K, Fredriksen Å, Ueland PM, et al. Folate and one-carbon metabolism gene polymorphisms and their associations with oral facial clefts. Am J Med Genet A 2008; 146A(4): 440-9.
Palmieri A, Masiero E, Martinelli M, Scapoli L, Pezzetti F, Caramelli E, et al. The MTHFD1 gene is not involved in cleft lip with or without palate onset among the Italian population. Hum Genet 2008; 72(3):297-9. https://doi.org/10.1111/j.1469-1809.2007. 00428.x
Bufalino A, Paranaiba LMR, De Aquino SN, Martelli-Junior H, Swerts MSO, Coletta RD. Maternal polymorphisms in folic acid metabolic genes are associated with nonsyndromic cleft lip and/or palate in the Brazilian population. Birth Defects Res A 2010; 88:980-6.
De Aquino SN, Hoshi R, Bakordakis E, Pucciarelli MGR, Messetti AC, Moreira H, et al. MTHFR rs2274976 polymorphism is a risk marker for nonsyndromic cleft lip with or without cleft palate in the Brazilian population. Birth Defects Res A 2014; 100:30-5.
Mills JL, Molloy AM, Parle-McDermott A, Troendle JF, Brody LC, Conley MR, et al. Folate-related gene polymorphisms as risk factors for cleft lip and cleft palate. Birth Defects Res A 2008; 82:636-43.
Zhao H, Zhang J, Zhang M, Deng F, Zheng L, Zheng H, et al. Is MTHFD1 polymorphism rs2236225 (c. 1958G>A) associated with the susceptibility of NSCL/P? A systematic review and meta-analysis. F1000Research 2015, 4:142. https://doi.org/10.12688/f1000research.6425.2
Mossey PA, Little J, Steegers-Theunissen R, Molloy A, Peterlin B, Shaw WC, et al. Genetic interactions in nonsyndromic orofacial clefts in Europe - EUROCRAN study. Cleft Palate Craniofac J 2017; 54(6):623-30. https://doi.org/10.1597/16-037
Luo YL, Cheng YL, Ye P, Wang W, Xiao H, Chen Q. Association between MTHFR polymorphisms and orofacial clefts risk: a meta-analysis. Birth Defects Res A 2012; 94:237-44.
Butali A, Little J, Chevrier C, Cordier S, Steegers-Theunissen R, Jugessur S, et al. Folic acid supplementation use and the MTHFR C667T polymorphism in orofacial clefts etiology: an individual participant data pooled-analysis. Birth Defects Res A 2013; 97:509-14.
How to Cite
Copyright (c) 2021 Pesquisa Brasileira em Odontopediatria e Clínica Integrada
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.