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


METHODS
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 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).


CONCLUSIONS
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.
School of Environmental and Life Sciences, Biomedical Sciences and Pharmacy, Maths and Physical Sciences, University of Newcastle, PO Box 127, Brush Road, Ourimbah, NSW 2258, Australia, The Pennsylvania State University, Anthropology Department, 409 Carpenter Building, University Park, PA 16802, USA, and Teaching and Research Unit, Central Coast Local Health District, PO Box 361, Gosford, NSW 2250, Australia.
Mark
M
Lucock
Zoë
Z
Yates
Charlotte
C
Martin
Jeong-Hwa
JH
Choi
Lyndell
L
Boyd
Sa
S
Tang
Nenad
N
Naumovski
John
J
Furst
Paul
P
Roach
Nina
N
Jablonski
George
G
Chaplin
Martin
M
Veysey
UV; UV-R exposure; VDR; folate; hypertension; insulin; melanization; photoperiod; pigmentation; serine hydroxymethyltransferase; solar cycle; thymidylate synthase; vitamin D