Bioinformatic and Genetic Association Analysis of MicroRNA Target Sites in One-Carbon Metabolism Genes

• DOI: 10.1371/journal.pone.0021851
• Publication Date: 2011-07-12T20:53:10Z
• Authors: Nicole Stone; Faith Pangilinan; Anne M. Molloy; Barry Shane; John M. Scott; Per Magne Ueland; James L. Mills; Peader N. Kirke; Praveen Sethupathy; Lawrence C. Brody
• Keywords: Genome-wide Association Study

One-carbon metabolism (OCM) is linked to DNA synthesis and methylation, amino acid cell proliferation. OCM dysfunction has been associated with increased risk for various diseases, including cancer neural tube defects. MicroRNAs (miRNAs) are ∼22 nt RNA regulators that have implicated in a wide array of basic cellular processes, such as differentiation metabolism. Accordingly, mis-regulation miRNA expression and/or activity can underlie complex disease etiology. We examined the possibility regulation by miRNAs. Using computational target prediction methods Monte-Carlo based statistical analyses, we identified two candidate "master regulators" (miR-22 miR-125) one pair co-regulators" (miR-344-5p/484 miR-488) may influence significant number genes involved OCM. Interestingly, miR-22 miR-125 significantly up-regulated cells grown under low-folate conditions. In complementary analysis, 15 single nucleotide polymorphisms (SNPs) located within predicted sites genes. genotyped these SNPs population healthy individuals (age 18–28, n = 2,506) was previously phenotyped serum metabolites related Prior correction multiple testing, detected associations between TCblR rs9426 methylmalonic (p 0.045), total homocysteine levels (tHcy) 0.033), B12 < 0.0001), holo transcobalamin 0.0001) 0.0001); MTHFR rs1537514 red blood folate 0.0001). However, upon further genetic determined each case, missense SNP more likely causative variant. Nonetheless, our silico simulations suggest miRNAs could play an important role