Gender and Single Nucleotide Polymorphisms inMTHFR,BHMT,SPTLC1,CRBP2,CETP, andSCARB1Are Significant Predictors of Plasma Homocysteine Normalized by RBC Folate in Healthy Adult

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.

WITHDRAWN: Association of homocysteine-metabolizing enzyme gene polymorphisms and lipid profiles: an investigation of a geneenvironment interaction

“…The interaction term for the MTHFR 677TT genotype and gender was also significant for TC and LDL-C levels (P = 0.0147 and 0.0243 for interaction, respectively). Similar to our findings, a previous study [30]. found interactions on the multiplicative scale between gender and Hcy/lipid-related SNPs on log-transformed plasma Hcy levels.…”

Ingestão de folato nos períodos pré e pós-fortificação mandatória: estudo de base populacional em São Paulo, Brasil

“…No Brasil, estudos registraram uma frequência do homozigoto TT entre 9,5-10% 53,54 . Sabe-se que a presença do polimorfismo C677T no gene da MTHFR está associada à diminuição da atividade da enzima, elevação sanguínea de homocisteína e ao risco aumentado da ocorrência de agravos cardiovasculares, neoplasias e outras doenças, e que o estado nutricional adequado da vitamina parece modular esta associação 55 . Achados como esses reforçam a importância de uma ingestão adequada às necessidades individuais.…”

Factores Determinantes Del Estado Nutricional Del Folato Y El Rol De La Variante Genética C677t De La Enzima Metilen Tetrahidrofolato Reductasa -MTHFR-

“…Aunque son muchas las moléculas implicadas en los ciclos del folato y la metionina, los polimorfismos del gen de la MTHFR han sido de gran interés por las asociaciones encontradas con indicadores bioquímicos del estado del folato y la homocisteína (26)(27)(28)(29)(30)(31).…”