Independent and Interactive Influences of Environmental UVR, Vitamin D Levels, and Folate Variant <i>MTHFD1</i>-rs2236225 on Homocysteine Levels

• Main Authors: Patrice Jones, Mark Lucock, Charlotte Martin, Rohith Thota, Manohar Garg, Zoe Yates, Christopher J. Scarlett, Martin Veysey, Emma Beckett
• Format: Article
• Language: English
• Published: MDPI AG 2020-05-01
• Series: Nutrients
• Subjects: homocysteine; folate; vitamin D; ultraviolet radiation; genetic variant
• Online Access: https://www.mdpi.com/2072-6643/12/5/1455

Elevated homocysteine (Hcy) levels are a risk factor for vascular diseases. Recently, increases in ultraviolet radiation (UVR) have been linked to decreased Hcy levels. This relationship may be mediated by the status of UVR-responsive vitamins, vitamin D and folate, and/or genetic variants influencing their levels; however, this has yet to be examined. Therefore, the independent and interactive influences of environmental UVR, vitamin D and folate levels and related genetic variants on Hcy levels were examined in an elderly Australian cohort (<i>n</i> = 619). Red blood cell folate, 25-hydroxyvitamin D (25(OH)D), and plasma Hcy levels were determined, and genotyping for 21 folate and vitamin D-related variants was performed. Erythemal dose rate accumulated over six-weeks (6W-EDR) and four-months (4M-EDR) prior to clinics were calculated as a measure of environmental UVR. Multivariate analyses found interactions between 6W-EDR and 25(OH)D levels (p_interaction = 0.002), and 4M-EDR and <i>MTHFD1</i>-rs2236225 (p_interaction = 0.006) in predicting Hcy levels. The association between 6W-EDR and Hcy levels was found only in subjects within lower 25(OH)D quartiles (<33.26 ng/mL), with the association between 4M-EDR and Hcy occurring only in subjects carrying the <i>MTHFD1</i>-rs2236225 variant. 4M-EDR, 6W-EDR, and <i>MTHFD1</i>-rs2236225 were also independent predictors of Hcy. Findings highlight nutrient–environment and gene–environment interactions that could influence the risk of Hcy-related outcomes.