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

• Published in: Evolution, medicine, and public health Vol. 2014; no. 1; pp. 69 - 91
• Main Authors: Lucock, Mark, Yates, Zoë, Martin, Charlotte, Choi, Jeong-Hwa, Boyd, Lyndell, Tang, Sa, Naumovski, Nenad, Furst, John, Roach, Paul, Jablonski, Nina, Chaplin, George, Veysey, Martin
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 02.04.2014
• Subjects: Original; UV; insulin; VDR; vitamin D; UV-R exposure; thymidylate synthase; serine hydroxymethyltransferase; melanization; pigmentation; folate; solar cycle; photoperiod; hypertension
• ISSN: 2050-6201; 2050-6201
• DOI: 10.1093/emph/eou013

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. 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. 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 C1420T-SHMT (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 VDR-Tru9I and 2R3R-TS genotypes (P = 0.0120 and 0.0360, respectively). 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.