TY - JOUR
T1 - Genetic variation in folylpolyglutamate synthase and gamma-glutamyl hydrolase and plasma homocysteine levels in the Singapore Chinese Health Study
AU - Oppeneer, Sarah J.
AU - Ross, Julie A
AU - Koh, Woon Puay
AU - Yuan, Jian Min
AU - Robien, Kim
PY - 2012/1
Y1 - 2012/1
N2 - The enzymes folylpolyglutamate synthase (FPGS) and gamma-glutamyl hydrolase (GGH) are essential for determining intracellular folate availability for one-carbon metabolism (OCM) pathways. FPGS adds glutamyl groups to the folate molecule, thereby converting folate into the preferred substrate for several enzymes in OCM pathways. GGH removes glutamyl groups, allowing folate metabolites to leave the cell. The purpose of this study was to evaluate whether single nucleotide polymorphisms (SNPs) in the. FPGS and. GGH genes influence measured plasma homocysteine levels. Study participants were a sub-cohort (n = 482) from the Singapore Chinese Health Study. SNPs were selected using HapMap tagSNPs and SNPs previously reported in the scientific literature. Multiple linear regression was used to evaluate the association between individual SNPs and plasma homocysteine levels. Two. FPGS (rs10106, rs1098774) and 9. GGH (rs719235, rs1031552, rs1800909, rs3758149, rs3780126, rs3824333, rs4617146, rs11545076, rs11545078) SNPs were included in the final analysis. Neither of the. FPGS SNPs, but three. GGH SNPs were associated with plasma homocysteine levels: rs11545076 (p = 0.001), rs1800909 (p = 0.02), and rs3758149 (p = 0.006). Only one (rs11545076) remained statistically significant after adjusting for multiple comparisons. This study suggests that. GGH SNPs, rs11545076, rs1800909, and rs3758149, may have functional relevance and result in alterations in plasma homocysteine levels. Since this is one of the first studies to assess. FPGS and. GGH genetic variants in relation to plasma homocysteine, further research is needed to confirm these findings and characterize the functional effects of these variants.
AB - The enzymes folylpolyglutamate synthase (FPGS) and gamma-glutamyl hydrolase (GGH) are essential for determining intracellular folate availability for one-carbon metabolism (OCM) pathways. FPGS adds glutamyl groups to the folate molecule, thereby converting folate into the preferred substrate for several enzymes in OCM pathways. GGH removes glutamyl groups, allowing folate metabolites to leave the cell. The purpose of this study was to evaluate whether single nucleotide polymorphisms (SNPs) in the. FPGS and. GGH genes influence measured plasma homocysteine levels. Study participants were a sub-cohort (n = 482) from the Singapore Chinese Health Study. SNPs were selected using HapMap tagSNPs and SNPs previously reported in the scientific literature. Multiple linear regression was used to evaluate the association between individual SNPs and plasma homocysteine levels. Two. FPGS (rs10106, rs1098774) and 9. GGH (rs719235, rs1031552, rs1800909, rs3758149, rs3780126, rs3824333, rs4617146, rs11545076, rs11545078) SNPs were included in the final analysis. Neither of the. FPGS SNPs, but three. GGH SNPs were associated with plasma homocysteine levels: rs11545076 (p = 0.001), rs1800909 (p = 0.02), and rs3758149 (p = 0.006). Only one (rs11545076) remained statistically significant after adjusting for multiple comparisons. This study suggests that. GGH SNPs, rs11545076, rs1800909, and rs3758149, may have functional relevance and result in alterations in plasma homocysteine levels. Since this is one of the first studies to assess. FPGS and. GGH genetic variants in relation to plasma homocysteine, further research is needed to confirm these findings and characterize the functional effects of these variants.
KW - FPGS
KW - Folate
KW - GGH
KW - Homocysteine
KW - SNP
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U2 - 10.1016/j.ymgme.2011.09.035
DO - 10.1016/j.ymgme.2011.09.035
M3 - Article
C2 - 22018726
AN - SCOPUS:84855360155
SN - 1096-7192
VL - 105
SP - 73
EP - 78
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 1
ER -