Article Text

other Versions

PDF
Associations of folate and choline metabolism gene polymorphisms with orofacial clefts
  1. Adrianna Mostowska (amostowska{at}wp.pl)
  1. Department of Biochemistry and Molecular Biology, University of Medical Sciences in Poznan, Poland
    1. Kamil K Hozyasz (khozyasz{at}verco.com.pl)
    1. Department of Paediatrics, Institute of Mother and Child in Warsaw, Poland
      1. Piotr Wojcicki (p.wojcicki{at}chirurgiaplastyczna.biz.pl)
      1. Univ Clinic of Med Academy in Wroclaw, Dept of Plastic Surgery Specialist Med Center in Polanica Zdr, Poland
        1. Maja Dziegelewska (maja_d{at}o2.pl)
        1. Department of Biochemistry and Molecular Biology, University of Medical Sciences in Poznan, Poland
          1. Pawel P Jagodzinski (pjagodzi{at}ump.edu.pl)
          1. Department of Biochemistry and Molecular Biology, University of Medical Sciences in Poznan, Poland

            Abstract

            Background: Nonsyndromic isolated cleft lip with or without cleft palate (NCL/P) is a common congenital anomaly in humans, the aetiology of which is complex and associated with both genetic and environmental factors. It has been reported that maternal nutritional factors are likely to play a major role in development of NCL/P in the embryo.

            Objective: As the mechanism by which folic acid and choline supplementation prevents NCL/P is poorly understood, we investigated the relationship between 16 polymorphic variants of 12 genes encoding enzymes involved in the metabolism of these two nutrients and the risk of facial clefts.

            Results: We found that individuals with the AA genotype of the BHMT rs3733890 polymorphism have a significantly lower risk of orofacial clefts (OR=0.1450; 95%CI: 0.0420-0.4995; p=0.0005; pcorr=0,008). We also demonstrate that the rs7639752 polymorphism of the PCYT1A gene increases the risk of NCL/P nearly twofold in the Polish population (OR=1.891; 95%CI: 1.151-3.107; p=0.011), but this association would not withstand correction for multiple testing (pcorr=0,176). The genetic variations in CBS, MTHFD1, MTHFR, MTR, MTRR, TCN2, BHMT2, CHDH, CHKA and PEMT were not separately correlated with NCL/P risk. However, the Multifactor Dimensionality Reduction (MDR) analysis showed a significant epistatic interaction between MTHFR (rs1801133), MTR (rs1805087) and PEMT (rs4646406) in NCL/P susceptibility.

            Conclusion: This study demonstrates that choline metabolism may play an important role in the aetiology of NCL/P. Polymorphic variants of BHMT and PCYT1A and interactions between genes of choline and folate metabolism might influence the risk of NCL/P in the Polish population.

            Statistics from Altmetric.com

            • Web Only Data

              Files in this Data Supplement:

            Request permissions

            If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.