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Genetic and lifestyle variables associated with homocysteine concentrations and the distribution of folate derivatives in healthy premenopausal women.
Summers, Carolyn M; Mitchell, Laura E; Stanislawska-Sachadyn, Anna; Baido, Shirley F; Blair, Ian A; Von Feldt, Joan M; Whitehead, Alexander S.
Afiliação
  • Summers CM; Centers for Cancer Pharmacology, Pharmacogenetics, and Excellence in Environmental Toxicology, Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Birth Defects Res A Clin Mol Teratol ; 88(8): 679-88, 2010 Aug.
Article em En | MEDLINE | ID: mdl-20544798
ABSTRACT

BACKGROUND:

Low folate and high homocysteine (Hcy) concentrations are associated with pregnancy-related pathologies such as spina bifida. Polymorphisms in folate/Hcy metabolic enzymes may contribute to this potentially pathogenic biochemical phenotype.

METHODS:

The study comprised 26 Caucasian and 23 African-American premenopausal women. Subjects gave fasting blood samples for biochemical phenotyping and genotyping. Total Hcy (tHcy) and both plasma and red blood cell (RBC) folate derivatives (i.e. tetrahydrofolate [THF], 5-methylTHF [5-MTHF], and 5,10-methenylTHF [5,10-MTHF]) were measured using stable isotope dilution liquid chromatography, multiple reaction monitoring, and mass spectrometry. Eleven polymorphisms from nine folate/Hcy pathway genes were genotyped. Tests of association between genetic, lifestyle, and biochemical variables were applied.

RESULTS:

In African American women, tHcy concentrations were associated (p < 0.05) with total RBC folate, RBC 5-MTHF, B(12), and polymorphisms in methionine synthase (MTR) and thymidylate synthase (TYMS). In Caucasian women, tHcy concentrations were not associated with total folate levels, but were associated (p < 0.05) with RBC THF, ratios of RBC 5-MTHFTHF, and polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR) and MTR. In African Americans, folate derivative levels were associated with smoking, B(12), and polymorphisms in MTR, TYMS, methionine synthase reductase (MTRR), and reduced folate carrier1 (RFC1). In Caucasians, folate derivative levels were associated with vitamin use, B(12), and polymorphisms in MTHFR, TYMS, and RFC1.

CONCLUSIONS:

Polymorphisms in the folate/Hcy pathway are associated with tHcy and folate derivative levels. In African American and Caucasian women, different factors are associated with folate/Hcy phenotypes and may contribute to race-specific differences in the risks of a range of pregnancy-related pathologies.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pré-Menopausa / Homocisteína / Estilo de Vida Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Middle aged / Pregnancy Idioma: En Revista: Birth Defects Res A Clin Mol Teratol Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pré-Menopausa / Homocisteína / Estilo de Vida Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Middle aged / Pregnancy Idioma: En Revista: Birth Defects Res A Clin Mol Teratol Ano de publicação: 2010 Tipo de documento: Article País de afiliação: Estados Unidos