Screening of polymorphisms for MTHFR and DHFR genes in spina bifida children and their mothers

M. Z. Husna, Endom Ismail, Sharaf Ibrahim, Amaramalar Selvi Naicker, H. Fakhrurazi, R. Ohnmar Htwe, Y. Kanehaswari, Abdul Halim Abd Rashid, Sau Wei Wong, K. Subashini, O. Nur Syahira, S. Aishah

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Mechanism underlying the beneficial effect of folic acid supplementation in reducing the risk of neural tube defect is still not well understood. Current evidences show the involvement of folic acid metabolic genes polymorphism as contributing factors that regulate this pathway. Therefore, the objective of this research was to determine the presence of C677T polymorphism for methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR-19 bp deletion) genes between mother-children pairs of case and control. With the approval of UKMMC ethic committee, genomic DNA was extracted from one hundred and forty consented bloods. Polymerase chain reaction (PCR), PCRRFLP (Restriction Fragment Length Polymorphism) and sequencing were employed to verify each nucleotide change. Our result shows that mutant MTHFR and DHFR alleles are present in all Malaysian sub-ethnic groups, case and control. Even though mutant MTHFR are found to be slightly higher in the case groups, 75% of the affected child is a non carrier for this allele and 62.5% of the mothers with an affected child are genotypically normal. For DHFR, almost all (87.5-100%) investigated samples are a carrier or having a double DHFR deletion be it a case or control pairs. However, strong maternal inheritance shown by the deleted allele might be due to a cascade effect of lacks of folate consumption or maternal uniparental disomy. In conclusion, the use of MTHFR and DHFR as markers in determining the risk of having spina bifida baby is uninformative and plays a small indirect role as the genetic causes of spina bifida. Therefore, spina bifida remains etiologically unknown polygenic and quantitative developmental trait whereby the searches for positive genetic marker need to be continued.

Original languageEnglish
Title of host publicationAIP Conference Proceedings
Pages271-276
Number of pages6
Volume1571
DOIs
Publication statusPublished - 2013
Event2013 UKM Faculty of Science and Technology Post-Graduate Colloquium - Selangor
Duration: 3 Jul 20134 Jul 2013

Other

Other2013 UKM Faculty of Science and Technology Post-Graduate Colloquium
CitySelangor
Period3/7/134/7/13

Fingerprint

polymorphism
folic acid
genes
deletion
screening
markers
ethics
polymerase chain reaction
sequencing
nucleotides
blood
constrictions
cascades
deoxyribonucleic acid
fragments
tubes
causes
defects

Keywords

  • Folic acid and polymorphisms
  • Neural tube defect
  • Spina bifida

ASJC Scopus subject areas

  • Physics and Astronomy(all)

Cite this

Husna, M. Z., Ismail, E., Ibrahim, S., Selvi Naicker, A., Fakhrurazi, H., Htwe, R. O., ... Aishah, S. (2013). Screening of polymorphisms for MTHFR and DHFR genes in spina bifida children and their mothers. In AIP Conference Proceedings (Vol. 1571, pp. 271-276) https://doi.org/10.1063/1.4858667

Screening of polymorphisms for MTHFR and DHFR genes in spina bifida children and their mothers. / Husna, M. Z.; Ismail, Endom; Ibrahim, Sharaf; Selvi Naicker, Amaramalar; Fakhrurazi, H.; Htwe, R. Ohnmar; Kanehaswari, Y.; Abd Rashid, Abdul Halim; Wong, Sau Wei; Subashini, K.; Syahira, O. Nur; Aishah, S.

AIP Conference Proceedings. Vol. 1571 2013. p. 271-276.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Husna, MZ, Ismail, E, Ibrahim, S, Selvi Naicker, A, Fakhrurazi, H, Htwe, RO, Kanehaswari, Y, Abd Rashid, AH, Wong, SW, Subashini, K, Syahira, ON & Aishah, S 2013, Screening of polymorphisms for MTHFR and DHFR genes in spina bifida children and their mothers. in AIP Conference Proceedings. vol. 1571, pp. 271-276, 2013 UKM Faculty of Science and Technology Post-Graduate Colloquium, Selangor, 3/7/13. https://doi.org/10.1063/1.4858667
Husna, M. Z. ; Ismail, Endom ; Ibrahim, Sharaf ; Selvi Naicker, Amaramalar ; Fakhrurazi, H. ; Htwe, R. Ohnmar ; Kanehaswari, Y. ; Abd Rashid, Abdul Halim ; Wong, Sau Wei ; Subashini, K. ; Syahira, O. Nur ; Aishah, S. / Screening of polymorphisms for MTHFR and DHFR genes in spina bifida children and their mothers. AIP Conference Proceedings. Vol. 1571 2013. pp. 271-276
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abstract = "Mechanism underlying the beneficial effect of folic acid supplementation in reducing the risk of neural tube defect is still not well understood. Current evidences show the involvement of folic acid metabolic genes polymorphism as contributing factors that regulate this pathway. Therefore, the objective of this research was to determine the presence of C677T polymorphism for methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR-19 bp deletion) genes between mother-children pairs of case and control. With the approval of UKMMC ethic committee, genomic DNA was extracted from one hundred and forty consented bloods. Polymerase chain reaction (PCR), PCRRFLP (Restriction Fragment Length Polymorphism) and sequencing were employed to verify each nucleotide change. Our result shows that mutant MTHFR and DHFR alleles are present in all Malaysian sub-ethnic groups, case and control. Even though mutant MTHFR are found to be slightly higher in the case groups, 75{\%} of the affected child is a non carrier for this allele and 62.5{\%} of the mothers with an affected child are genotypically normal. For DHFR, almost all (87.5-100{\%}) investigated samples are a carrier or having a double DHFR deletion be it a case or control pairs. However, strong maternal inheritance shown by the deleted allele might be due to a cascade effect of lacks of folate consumption or maternal uniparental disomy. In conclusion, the use of MTHFR and DHFR as markers in determining the risk of having spina bifida baby is uninformative and plays a small indirect role as the genetic causes of spina bifida. Therefore, spina bifida remains etiologically unknown polygenic and quantitative developmental trait whereby the searches for positive genetic marker need to be continued.",
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