Human Genetics

, Volume 123, Issue 3, pp 289–295

An insertion/deletion polymorphism of the dihydrofolate reductase (DHFR) gene is associated with serum and red blood cell folate concentrations in women

  • Anna Stanisławska-Sachadyn
  • Karen S. Brown
  • Laura E. Mitchell
  • Jayne V. Woodside
  • Ian S. Young
  • John M. Scott
  • Liam Murray
  • Colin A. Boreham
  • Helene McNulty
  • J. J. Strain
  • Alexander S. Whitehead
Original Investigation

DOI: 10.1007/s00439-008-0475-y

Cite this article as:
Stanisławska-Sachadyn, A., Brown, K.S., Mitchell, L.E. et al. Hum Genet (2008) 123: 289. doi:10.1007/s00439-008-0475-y

Abstract

A low serum folate and high homocysteine phenotype is associated with an increased risk of neural tube defects (NTDs), cardiovascular diseases and other pathologies. Thus defining both genetic and non-genetic factors that may impact folate/homocysteine metabolism will enhance our understanding of the etiologic mechanisms underlying these conditions and facilitate risk assessment. Dihydrofolate reductase catalyzes the reduction of folic acid to dihydrofolate and thereafter to tetrahydrofolate. The impact of the dihydrofolate reductase (DHFR) c.86 + 60_78 insertion/deletion (ins/del) polymorphism on folate and homocysteine concentrations was analyzed using data from healthy young adults from Northern Ireland, collected as part of visit three of the Young Hearts Project. Among men the DHFR c.86 + 60_78 polymorphism was not significantly associated with serum or red blood cell folate concentrations, or with homocysteine concentrations. Among women the DHFR c.86 + 60_78 polymorphism explained 2% of the variation in RBC folate levels and 5% of the variation in serum folate levels, but did not appear to have an independent effect on homocysteine. Relative to women with the DHFR c.86 + 60_78 ins/ins and ins/del genotypes, del/del homozygotes had increased serum and red blood cell folate concentrations and may therefore be at decreased risk of having offspring affected by NTDs and of other adverse reproductive and health outcomes attributable to low folate.

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Anna Stanisławska-Sachadyn
    • 1
  • Karen S. Brown
    • 1
  • Laura E. Mitchell
    • 2
  • Jayne V. Woodside
    • 3
  • Ian S. Young
    • 3
  • John M. Scott
    • 4
  • Liam Murray
    • 3
  • Colin A. Boreham
    • 5
  • Helene McNulty
    • 6
  • J. J. Strain
    • 6
  • Alexander S. Whitehead
    • 1
  1. 1.Department of Pharmacology and Center for PharmacogeneticsUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  2. 2.Institute of Biosciences and TechnologyThe Texas A&M University System, Health Science CenterHoustonUSA
  3. 3.Cardiovascular Research CentreQueen’s University BelfastBelfastNorthern Ireland
  4. 4.Department of Clinical MedicineTrinity CollegeDublinIreland
  5. 5.Institute for Sport and HealthUniversity CollegeDublinIreland
  6. 6.Northern Ireland Centre for Food and HealthUniversity of UlsterColeraineNorthern Ireland