SNPs affect folate metabolism in study of Puerto-Ri...( BOSTON (November 10 2008) Researche...)

BOSTON (November 10, 2008) Researchers at Tufts University have gained further understanding of the genomic basis for altered folate metabolism and the content of uracil in blood DNA. In a study published in October's American Journal of Clinical Nutrition, senior author Jimmy Crott, PhD, and colleagues studied nine single nucleotide polymorphisms (SNPs) in five genes involved in folate uptake and retention: folate hydrolase (FOLH1), folate polyglutamate synthase (FPGS), γ-glutamyl hyrdolase (GGH), proton-coupled folate transporter (PCFT), and reduced folate carrier (RFC1) in a cohort of 991 Puerto Rican adults residing in and around Boston. In addition, four SNPs in two genes involved in folate metabolism previously associated with altered blood folate and homocysteine concentrations were studied: methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR).

SNPs are variations in the sequence of nucleotides, or building blocks, that make up genes. Humans possess two copies of every gene. For each SNP, there are three possible genotypes depending on the presence of "normal" and "variant" copies of the gene; two normal copies, one normal and one variant or two variant copies.

Diseases, such as some cancers, have been associated with diminished blood folate concentrations and abnormal folate metabolism. Crott, a scientist in the Vitamins and Carcinogenesis Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts, and first author Lauren DeVos of Pennsylvania State University found that several SNPs affect folate metabolism, as evidenced by altered concentrations of blood homocysteine, folate, and DNA uracil.

"Perhaps the most intriguing results of this study involve these SNPs that affected the concentration of uracil in DNA. Uracil accumulation has the potential to cause DNA breakage, a mutagenic event that may increase the risk for cancer," Crott said.

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