title: Gender and single nucleotide polymorphisms in MTHFR, BHMT, SPTLC1, CRBP2, CETP, and SCARB1 are significant predictors of plasma homocysteine normalized by RBC folate in healthy adults.
abstract: Using linear regression models, we studied the main and 2-way interaction effects of the predictor variables gender, age, BMI, and 64 folate/vitamin B-12/homocysteine (Hcy)/lipid/cholesterol-related single nucleotide polymorphisms (SNP) on log-transformed plasma Hcy 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 P values 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 × MTHFR (rs1801131; P = 0.012), gender × CRBP2 (rs2118981; P = 0.011), and gender × 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 Hcy and genetic regulation is important, because Hcy may be related to inflammation, obesity, cardiovascular disease, and diabetes mellitus. We conclude that gender and SNP significantly affect nHcy.
authors: Department of Nutrition, University of California, Davis, CA, USA. ajclifford@ucdavis.edu
authors: Andrew J
authors: AJ
authors: Clifford
authors: Kehui
authors: K
authors: Chen
authors: Laura
authors: L
authors: McWade
authors: Gonzalo
authors: G
authors: Rincon
authors: Seung-Hyun
authors: SH
authors: Kim
authors: Dirk M
authors: DM
authors: Holstege
authors: Janel E
authors: JE
authors: Owens
authors: Bitao
authors: B
authors: Liu
authors: Hans-Georg
authors: HG
authors: Müller
authors: Juan F
authors: JF
authors: Medrano
authors: James G
authors: JG
authors: Fadel
authors: Alanna J
authors: AJ
authors: Moshfegh
authors: David J
authors: DJ
authors: Baer
authors: Janet A
authors: JA
authors: Novotny
mesh_terms: D000328:Adult; D000368:Aged; D050940:Betaine-Homocysteine S-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics* / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011237:Predictive Value of Tests; D012016:Reference Values; D054840:Retinol-Binding Proteins, Cellular / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D051122:Scavenger Receptors, Class B / Q000235:genetics* / Q000378:metabolism; D051102:Serine C-Palmitoyltransferase / Q000235:genetics* / Q000378:metabolism; D017678:Sex Distribution
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; C518459:RBP2 protein, human; D054840:Retinol-Binding Proteins, Cellular; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D006710:Homocysteine; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C494548:BHMT protein, human; D050940:Betaine-Homocysteine S-Methyltransferase; C487784:SPTLC1 protein, human; D051102:Serine C-Palmitoyltransferase