Frequency of folate-related polymorphisms varies by skin pigmentation

Objectives: Folate-mediated 1-carbon transfer processes are vital in human health but are susceptible to independent and interactive influences of genetic variance and environmental exposures. Evidence suggests folate levels may be impacted by genetic variance and environmental UVR, with the effect of UVR levels influenced in part by degree of skin pigmentation. Folate-related genes are also influenced by UVR levels; however, the potential relationship between key folate-related genes and skin pigmentation has not yet been explored. The purpose of this study was to examine potential associations between frequencies of key folate variants and degree of skin pigmentation. Methods: Association between population prevalence of 17 variants in 9 folate-related genes (MTRR, MTR, MTHFR, CBS, SHMT1, MTHFD1, RFC1, BHMT, TYMS) and the Fitzpatrick skin phototype of populations was assessed via collation of genotypic data from ALFRED (Allele Frequency Database) and 1000 Genomes databases. Results: A significant association between variant frequency and Fitzpatrick phototype was observed for 16 of 17 examined variants (P <.0029 Bonferroni corrected significance threshold in all cases). Conclusions: These findings demonstrate novel relationships between skin color and folate-related genes, with trends suggesting folate genotypes are selected to maintain homeostasis in the folate system under differing UVR conditions.