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.
Highlights
Folate is an essential nutrient with a major role in regulating homocysteine levels, a nonessential amino acid which at elevated levels is an independent risk factor for adverse health outcomes such as atherosclerosis, stroke and coronary artery disease [1]
Average red blood cell (RBC) folate, serum folate and homocysteine levels were within the normal ranges, defined as 317–1422 nmol/L for RBC
Serum folate is an indicator of short-term folate status, reflective of recent dietary intake, while RBC folate reflects long-term status as it is less influenced by recent dietary intake [45]. 4M-erythemal dose rate (EDR) was negatively associated with levels of both serum and RBC folate, indicating Ultraviolet radiation (UVR) as a potential environmental determinant of both short- and long-term folate status
Summary
Folate is an essential nutrient with a major role in regulating homocysteine levels, a nonessential amino acid which at elevated levels is an independent risk factor for adverse health outcomes such as atherosclerosis, stroke and coronary artery disease [1]. Folate acts as a key regulator of homocysteine levels through roles in converting homocysteine to essential amino acid, methionine, with an inverse relationship between folate and homocysteine levels well established [2,3]. Various environmental and genetic factors determine folate status [6], with potential consequences for health and disease risks. Many of these factors have been studied in. Public Health 2020, 17, 1545; doi:10.3390/ijerph17051545 www.mdpi.com/journal/ijerph
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