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Folate network genetic variation, plasma homocysteine, and global genomic methylation content
Author(s) -
Wernimont S M,
Smith E M,
Clark A G,
Stover P J,
Wells M T,
Litonjua A A,
Weiss S T,
Gaziano J M,
Tucker K L,
Baccarelli A,
Schwartz J,
Cassano P A
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.552.6
Subject(s) - single nucleotide polymorphism , methylation , genetics , dna methylation , biology , gene , homocysteine , methylenetetrahydrofolate reductase , genotyping , genotype , genome wide association study , epigenetics , gene expression , endocrinology
Sequence variants in genes of the folate network are hypothesized to cause differences in homocysteine and DNA methylation. We studied 334 SNPs in 52 network genes in relation to plasma homocysteine and global genomic methylation. SNPs were selected based on function and gene coverage, and genes were categorized based on role in the folate metabolic pathway. Age‐ and smoking‐adjusted general linear models estimated genotype—phenotype associations. 23 SNPs were associated with homocysteine levels (p≤0.05), 29 were associated with Alu methylation (p≤0.05), and 13 were associated with LINE‐1 methylation (p≤0.05). The absorption and transport, cytoplasmic, and mitochondrial genes had the most SNPs associated with homocysteine levels. The mitochondrial and cytoplasmic genes had the most SNPs associated with Alu, and cytoplasmic genes had the most SNPs associated with LINE‐1. MTHFR SNPs were significant predictors of all 3 outcomes, while ALDH1L1, CBS, CTH, DNMT1, MTHFD1L, SARDH , and TCN2 SNPs were significant predictors of 2 outcomes. The set of most significant SNPs that predicted homocysteine levels or Alu or LINE‐1 methylation was unique to each outcome. Funding: NIH T32 DK007158‐34 (SMW), G105 NHLBI Resequencing and Genotyping Service (PAC).