Distribution of functional 1‐carbon metabolism single nucleotide polymorphisms in Gambian versus European populations (827.4)

Abstract

Choline is an essential dietary nutrient and, along with its metabolites, has profound implications in cell signaling, methyl group donation, neurotransmitter synthesis, structural integrity of cell membranes, and fetal neurogenesis. Several important single nucleotide polymorphisms (SNPs) in the choline and folate metabolism pathways have been associated with organ dysfunction, either liver or muscle damage, in response to a low choline diet. A study was conducted to compare the distribution of these known functional SNPs in pregnant women in rural Gambia (N=248), a population with a low choline diet, versus a North Carolina population of European Descent (N=230), a population with a relatively high choline diet. The effect alleles of these SNPs increase dietary choline requirements and contribute to organ dysfunction. The prevalence of the effect allele of functional SNPs in 1‐carbon metabolism was significantly different in Gambian versus European populations: PEMT rs12325817 2.4% and 17.5%, MTHFD1 rs2236225 2.4% and 15.0 %; CHDH rs12676 0.0% and 9.4 % (P<0.0001). Interestingly, in the Gambian population, the effect alleles are reduced or absent as compared to the North Carolina population. This supports our current hypothesis that dietary choline intake is a novel selective pressure that could lead to the differences in SNP distribution and associated risk for organ dysfunction in these populations.Grant Funding Source: Supported by The Gates Foundation