Evidence of interaction between genes in the folate/homocysteine metabolic pathway in controlling risk of non-syndromic oral cleft.

Abstract

OBJECTIVE:

Little consistent evidence is available for the association between the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P) and any of the individual genes in the folate/homocysteine metabolic pathway. We investigated the genes in the folate pathway to further clarify its potential influence on the risk of NSCL/P considering gene-gene (G×G) interaction.

SUBJECTS AND METHODS:

We selected markers in 18 genes from the pathway and applied Cordell's method to test for G×G interaction using 1,908 NSCL/P case-parent trios ascertained in an international consortium where a genomewide association study (GWAS) of oral clefts was conducted.

RESULTS:

We found intriguing signals among Asian and European ancestry groups for G×G interaction between markers in betaine-homocysteine methyltransferase gene (BHMT/BHMT2) and dimethylglycine dehydrogenase gene (DMGDH) attaining genomewide significance. In the pooled data, the top significant interaction was found between rs13158309 (BHMT) and rs10514154 (DMGDH, p = 1.45 × 10-12 ).

CONCLUSIONS:

Our study illustrated the importance of taking into account potential G×G interaction for genetic association analysis in NSCL/P, and this study suggested both BHMT/BHMT2 and DMGDH should be considered as candidate genes for NSCL/P in future studies.

• Authors: P Wang, T Wu, H Schwender, H Wang, B Shi, Z Q Wang, Y Yuan, D J Liu, M Y Wang, J Li, Z B Zhou, H P Zhu, T H Beaty
• Journal: Oral diseases (Oral Dis) Vol. 24 Issue 5 Pg. 820-828 (Jul 2018) ISSN: 1601-0825 [Electronic] Denmark
• PMID: 29356306 (Publication Type: Journal Article)
• Copyright: © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

Chemical References

• BHMT2 protein, human
• Mitochondrial Proteins
• Homocysteine
• Folic Acid
• DMGDH protein, human
• Dimethylglycine Dehydrogenase
• BHMT protein, human
• Betaine-Homocysteine S-Methyltransferase

Topics

• Asian People (genetics)
• Betaine-Homocysteine S-Methyltransferase (genetics)
• Cleft Lip (genetics)
• Cleft Palate (genetics)
• Dimethylglycine Dehydrogenase (genetics)
• Epistasis, Genetic
• Folic Acid (metabolism)
• Genome-Wide Association Study
• Homocysteine (metabolism)
• Humans
• Linkage Disequilibrium
• Metabolic Networks and Pathways
• Mitochondrial Proteins (genetics)
• Polymorphism, Single Nucleotide
• Risk Factors
• White People (genetics)