Photoperiod at conception predicts C677T-MTHFR genotype: A novel gene-environment interaction.
Data is presented, which suggest that the day length a woman experiences during the periconceptional period predicts the C677T-MTHFR genotype of her child. Logistic regression analysis involving 375 neonates born in the same geographical location within a three year period demonstrated that photoperiod (minutes) at conception predicts both genotype (P = 0.0139) and mutant allele carriage (P = 0.0161); the trend clearly showing that the 677T-MTHFR allele frequency increases as photoperiod increases. We propose a number of explanations, including a hypothesis in which a long photoperiod around conception decreases maternal systemic folate because of UVA induced dermal oxidative degradation of 5-methyl-H(4)folate, leading to a lower cellular 5,10-methylene-H(4)folate status. In this scenario, 5,10-methylene-H(4)folate would be more efficiently used for dTMP and DNA synthesis by 677T-MTHFR embryos than wildtype embryos giving the 677T-MTHFR embryos increased viability, and hence increasing mutant T-allele frequency. Alternate hypotheses include: increased seasonal availability of folate rich foods that genetically buffer any negative effect of 677T-MTHFR in embryos; seasonal oxidative stress lowering embryo-toxic homocysteine; an undefined hormonal effect of photoperiod on the neuroendocrine axis, which mediates genotype/embryo selection. The effect of photoperiod on genotype seems clear, but the speculative molecular mechanism underpinning the effect needs careful examination.
Lucock
Mark
M
School of Environmental and Life Sciences, University of Newcastle, Ourimbah New South Wales 2258, Australia. Mark.Lucock@newcastle.edu.au
Glanville
Tracey
T
Ovadia
Liz
L
Yates
Zoë
Z
Walker
James
J
Simpson
Nigel
N
D004777:Environment; D005260:Female; D005306:Fertilization; D005492:Folic Acid / Q000378:metabolism*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009154:Mutation; D017440:Photoperiod; D011110:Polymorphism, Genetic; D011247:Pregnancy
D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)