title: Solar cycle predicts folate-sensitive neonatal genotypes at discrete phases of the first trimester of pregnancy: a novel folate-related human embryo loss hypothesis.
abstract: Folate, a key periconceptional nutrient, is ultraviolet light (UV-R) sensitive. We therefore hypothesise that a relationship exists between sunspot activity, a proxy for total solar irradiance (particularly UV-R) reaching Earth, and the occurrence of folate-sensitive, epigenomic-related neonatal genotypes during the first trimester of pregnancy. Limited data is provided to support the hypothesis that the solar cycle predicts folate-related human embryo loss: 379 neonates born at latitude 54°N between 1998 and 2000 were examined for three folate-sensitive, epigenome-related polymorphisms, with solar activity for trimester one accessed via the Royal Greenwich Observatory-US Air force/National Oceanic and Atmospheric Administration Sunspot Database (34,110 total observation days). Logistic regression showed solar activity predicts C677T-methylenetetrahydrofolate reductase (C677T-MTHFR) and A66G-methionine synthase reductase (A66G-MSR) genotype at discrete phases of trimester one. Total and maximal sunspot activity predicts C677T-MTHFR genotype for days 31-60 of trimester one (p=0.0181 and 0.0366, respectively) and A66G-MSR genotype for days 61-90 of trimester one (p=0.0072 and 0.0105, respectively). Loss of UV-R sensitive folate associated with the sunspot cycle might therefore interact with variant folate genes to perturb DNA methylation and/or elaboration of the primary base sequence (thymidylate synthesis), as well as increase embryo-toxic homocysteine. We hypothesise that this may influence embryo viability leading to 677CC-MTHFR and 66GG-MSR embryo loss at times of increased solar activity. This provides an interesting and plausible link between well recognised 'folate gene originated developmental disorders' and 'solar activity/seasonality modulated developmental disorders'.
authors.affiliation: School of Environmental & Life Sciences, University of Newcastle, P.O. Box 127, Brush Rd., Ourimbah, NSW 2258, Australia. Mark.Lucock@newcastle.edu.au
authors.forename: Mark
authors.initials: M
authors.lastname: Lucock
authors.forename: Tracey
authors.initials: T
authors.lastname: Glanville
authors.forename: Zoë
authors.initials: Z
authors.lastname: Yates
authors.forename: James
authors.initials: J
authors.lastname: Walker
authors.forename: John
authors.initials: J
authors.lastname: Furst
authors.forename: Nigel
authors.initials: N
authors.lastname: Simpson
mesh_terms: D002980:Climate; D020964:Embryo Loss / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008954:Models, Biological; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000235:genetics*; D015995:Prevalence; D012993:Solar Energy; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D005492:Folic Acid