Environmental UVR Levels and Skin Pigmentation Gene Variants Associated with Folate and Homocysteine Levels in an Elderly Cohort

Abstract

Ultraviolet radiation (UVR) is a ubiquitous exposure which may contribute to decreased folate levels. Skin pigmentation mediates the biological effect of UVR exposure, but its relationship to folate levels is unexamined. Interactions may exist between UVR and pigmentation genes in determining folate status, which may, in turn, impact homocysteine levels, a potential risk factor for multiple chronic diseases. Therefore, independent and interactive influences of environmental UVR and genetic variants related to skin pigmentation (MC1R-rs1805007, IRF4-rs12203592 and HERC2-rs12913832) on folate (red blood cell (RBC) and serum) and homocysteine levels were examined in an elderly Australian cohort (n = 599). Genotypes were assessed by RT/RFLP-PCR, and UVR exposures were assessed as the accumulated erythemal dose rate accumulated over 4 months (4M-EDR). Multivariate analysis found significant negative associations between 4M-EDR and RBC folate (p < 0.001, β = −0.19), serum folate (p = 0.045, β = −0.08) and homocysteine levels (p < 0.001, β = −0.28). Significant associations between MC1R-rs1805007 and serum folate levels (p = 0.020), and IRF4-rs12203592 and homocysteine levels (p = 0.026) occurred but did not remain significant following corrections with confounders. No interactions between 4M-EDR and pigmentation variants in predicting folate/homocysteine levels were found. UVR levels and skin pigmentation-related variants are potential determinants of folate and homocysteine status, although, associations are mixed and complex, with further studies warranted.

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

“…This study was a secondary analysis using samples and pre-existing data from the Retirement Health and Lifestyle Study (RHLS), a cross-sectional study examining the health and lifestyle of older Australians (>65 years) living in the Central Coast region of NSW, Australia (n = 650) [11,[26][27][28]. This Australian elderly cohort was an appropriate focus for this investigation and previous studies due to Australians, in general, being exposed to high levels of environmental UVR [29], with elderly Australians a sub-population particularly at risk of adverse UVR-related effects as biological photoprotective factors reduce with age [30].…”

“…H-2008-0431). Further details on the original study population and design have been reported previously [11,[26][27][28].…”

“…Information was gathered for the total amount of EDR accumulated over two time periods of interest-over the six weeks (6W-EDR) and four months (4M-EDR) prior to the subject's clinic appointments. 4M-EDR was assessed in a previous investigation examining relationships between environmental UVR and Hcy and/or RBC folate levels [11], and was chosen due to four months being the approximate lifespan of an RBC (i.e., relevant to RBC folate turnover), respectively. 6W-EDR was also assessed in the current study, with six weeks being indicative of the time-lag between UVR exposure and serum 25(OH)D changes [52,53].…”

“…EDR values ranged considerably between RHLS subjects and captured varying seasons due to original subject recruitments and clinic appointments spanning > 18 months (>80 clinic dates). Further details on the method have been published previously [11,54,55].…”

“…UVR exposure has been shown to cause the breakdown of folates in vitro [5,6], and increases in UVR exposure have been associated with a decreased folate status in several human cohort studies [6][7][8][9][10]. More recently, we have reported that increases in environmental UVR levels are also associated with decreases in Hcy levels [11]. This association is counter-intuitive given the well-known inverse relationship between folate and Hcy levels, but it may be modulated in part by folate-related genetic factors, which require further investigation.…”