Vitamin D, folate, and potential early lifecycle environmental origin of significant adult phenotypes

Mark Lucock, Zoe Yates, Charlotte Martin, Jeong-Hwa Choi, Lyndell Boyd, Sa Tang, Nenad NAUMOVSKI, John Furst, Paul Roach, Nina Jablonski, George Chaplin, Martin Veysey

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)
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Background and objectives: Vitamin D and folate are highly UV sensitive, and critical for maintaining health throughout the lifecycle. This study examines whether solar irradiance during the first trimester of pregnancy influences vitamin D receptor (VDR) and nuclear folate gene variant occurrence, and whether affected genes influence late-life biochemical/clinical phenotypes. Methodology: 228 subjects were examined for periconceptional exposure to solar irradiance, variation in vitamin D/folate genes (polymerase chain reaction (PCR)), dietary intake (food frequency questionnaire (FFQ)) and important adult biochemical/clinical phenotypes. Results: Periconceptional solar irradiance was associated with VDR-BsmI (P=0.0008 wk7), TaqI (P=0.0014 wk7) and EcoRV (P=0.0030 wk6) variant occurrence between post-conceptional weeks 6-8, a period when ossification begins. Similar effects were detected for other VDR gene polymorphisms. Periconceptional solar irradiance was also associated with 19 bp del-DHFR (P=0.0025 wk6), and to a lesser extent C1420T-SHMT (P=0.0249 wk6), a folate-critical time during embryogenesis. These same genes were associated with several late-life phenotypes: VDR-BsmI, TaqI and ApaI determined the relationship between dietary vitamin D and both insulin (P<0.0001/BB, 0.0007/tt and 0.0173/AA, respectively) and systolic blood pressure (P=0.0290/Bb, 0.0299/Tt and 0.0412/AA, respectively), making them important early and late in the lifecycle. While these and other phenotype associations were found for the VDR variants, folate polymorphism associations in later-life were limited to C1420TSHMT (P=0.0037 and 0.0297 for fasting blood glucose and HbA1c levels, respectively). We additionally report nutrient-gene relationships with body mass index, thiol/folate metabolome, cognition, depression and hypertension. Furthermore, photoperiod at conception influenced occurrence of VDRTru9I and 2R3R-TS genotypes (P=0.0120 and 0.0360, respectively). Conclusions and implications: Findings identify environmental and nutritional agents that may interact to modify gene-phenotype relationships across the lifecycle, offering new insight into human ecology. This includes factors related to both disease aetiology and the evolution of skin pigmentation.

Original languageEnglish
Article numbereou013
Pages (from-to)69-91
Number of pages23
JournalEvolution, Medicine and Public Health
Issue number1
Publication statusPublished - 2014
Externally publishedYes


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