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Effects of eight folate‐relevant polymorphisms on human blood folate and homocysteine
Author(s) -
Clifford Andrew J.,
Owens Janel Elizabeth,
Liu Bitao,
Müller HansGeorg,
Medrano Juan F.,
Fadel James G.,
Moghaddam Billur
Publication year - 2007
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.21.5.a121-a
Subject(s) - mtrr , methylenetetrahydrofolate reductase , single nucleotide polymorphism , homocysteine , genotype , population , genetics , snp , medicine , biology , endocrinology , gene , environmental health
Folate metabolism can be influenced by the following polymorphisms (SNPs): MTHFR C677T and A1298C, MTR A2756G, MTRR A66G, CBS T833C and 844ins68, GCP II C1561T, TC II C776G, and RFC1 A80G. Their influences have primarily been studied individually, so the main and interactive effects on blood traits are not well known. We screened 370 normal adults for the above SNPs, blood chemistries (RBC folate, plasma homocysteine (Hcy), vitamins B6 and B12, and lipids), and folate intake. We recorded gender, ethnicity/race, age, and BMI (population characteristics). Blood chemistries were used as response variables, while population characteristics and the eight genotypes were used as predictor variables in ANCOVA modeling and variable selection through the Akaike Information Criterion for subjects with complete records (n = 328). RBC folate increased with age, TCII CG, and the gender × RFC1 GG interaction (all p < 0.05). RBC folate decreased with the male gender, RFC1 AG and GG, and the age × MTRR GG interaction. Hcy, normalized by RBC folate, increased with age, male gender, MTRR GG, and RFC1 AG. It decreased with the male gender × RFC1 AG and GG interactions. The normalized Hcy of the Caucasian subset increased with male gender, and the interactive effects of TCII CG or GG × RFC1 AG or GG. It was decreased by the MTHFR 1298 AC, TC II CG and GG, RFC1 AG and GG, and the gender × RFC1 AG and GG interactions. MTR, CBS, and GCP II were without influence. NIH RO1 45939.