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Using linear regression models, we studied the main and 2-way interaction effects of the predictor variables gender, age, BMI, and 64 folateA/itamin B-12/homocysteine (Hcyl/lipid/cholesterol-related single nucleotide polymorphisms (SNP) on log-transformed plasma Hey normalized by RBC folate measurements (nHcy) in 373 healthy Caucasian adults (50% women). Variable selection was conducted by stepwise Akaike information criterion or least angle regression and both methods led to the same final model. Significant predictors (where Pvalues were adjusted for false discovery rate) included type of blood sample [whole blood (WB) vs. plasma-depleted WB; P < 0.001 ] used for folate analysis, gender (P< 0.001), and SNP in genes SPTLC1 (rs11790991 ; P= 0.040), CRBP2 (rs2118981 ; P< 0.001 ), BHMT (rs3733890; P = 0.019), and CETP (rs5882; P = 0.017). Significant 2-way interaction effects included gender x MTHFR (rs1801131 ; P= 0.012), gender x CRBP2 (rs2118981; P= 0.011), and gender X SCARB1 (rs83882; P= 0.003). The relation of nHcy concentrations with the significant SNP (SPTLC1, BHMT, CETP, CRBP2, MTHFR, and SCARB1) is of interest, especially because we surveyed the main and interaction effects in healthy adults, but it is an important area for future study. As discussed, understanding Hey and genetic regulation is important, because Hey may be related to inflammation, obesity, cardiovascular disease, and diabetes mellitus. We conclude that gender and SNP significantly affect nHcy. [ABSTRACT FROM AUTHOR]