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 journalArticle

19 Citations (Scopus)

Abstract

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
Volume2014
Issue number1
DOIs
Publication statusPublished - 2014
Externally publishedYes

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vitamin
vitamin D
Folic Acid
Vitamin D
folic acid
Calcitriol Receptors
phenotype
Phenotype
gene
Genes
irradiance
solar radiation
receptors
genes
polymorphism
Blood Pressure
Skin Pigmentation
blood
genetic polymorphism
Metabolome

Cite this

Lucock, M., Yates, Z., Martin, C., Choi, J-H., Boyd, L., Tang, S., ... Veysey, M. (2014). Vitamin D, folate, and potential early lifecycle environmental origin of significant adult phenotypes. Evolution, Medicine and Public Health, 2014(1), 69-91. [eou013]. https://doi.org/10.1093/emph/eou013
Lucock, Mark ; Yates, Zoe ; Martin, Charlotte ; Choi, Jeong-Hwa ; Boyd, Lyndell ; Tang, Sa ; NAUMOVSKI, Nenad ; Furst, John ; Roach, Paul ; Jablonski, Nina ; Chaplin, George ; Veysey, Martin. / Vitamin D, folate, and potential early lifecycle environmental origin of significant adult phenotypes. In: Evolution, Medicine and Public Health. 2014 ; Vol. 2014, No. 1. pp. 69-91.
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abstract = "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.",
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author = "Mark Lucock and Zoe Yates and Charlotte Martin and Jeong-Hwa Choi and Lyndell Boyd and Sa Tang and Nenad NAUMOVSKI and John Furst and Paul Roach and Nina Jablonski and George Chaplin and Martin Veysey",
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Lucock, M, Yates, Z, Martin, C, Choi, J-H, Boyd, L, Tang, S, NAUMOVSKI, N, Furst, J, Roach, P, Jablonski, N, Chaplin, G & Veysey, M 2014, 'Vitamin D, folate, and potential early lifecycle environmental origin of significant adult phenotypes', Evolution, Medicine and Public Health, vol. 2014, no. 1, eou013, pp. 69-91. https://doi.org/10.1093/emph/eou013

Vitamin D, folate, and potential early lifecycle environmental origin of significant adult phenotypes. / Lucock, Mark; Yates, Zoe; Martin, Charlotte; Choi, Jeong-Hwa; Boyd, Lyndell; Tang, Sa; NAUMOVSKI, Nenad; Furst, John; Roach, Paul; Jablonski, Nina; Chaplin, George; Veysey, Martin.

In: Evolution, Medicine and Public Health, Vol. 2014, No. 1, eou013, 2014, p. 69-91.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Vitamin D, folate, and potential early lifecycle environmental origin of significant adult phenotypes

AU - Lucock, Mark

AU - Yates, Zoe

AU - Martin, Charlotte

AU - Choi, Jeong-Hwa

AU - Boyd, Lyndell

AU - Tang, Sa

AU - NAUMOVSKI, Nenad

AU - Furst, John

AU - Roach, Paul

AU - Jablonski, Nina

AU - Chaplin, George

AU - Veysey, Martin

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Folate

KW - Hypertension

KW - Insulin

KW - Melanization

KW - Photoperiod

KW - Pigmentation

KW - Serine hydroxymethyltransferase

KW - Solar cycle

KW - Thymidylate synthase

KW - UV

KW - UV-R exposure

KW - VDR

KW - Vitamin D

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