title: Interactions among methylenetetrahydrofolate reductase (MTHFR) and cystathionine β-synthase (CBS) polymorphisms - a cross-sectional study: multiple heterozygosis as a risk factor for higher homocysteine levels and vaso-occlusive episodes.
abstract: High plasma homocysteine (Hcy) ​​levels may be responsible for vaso-occlusive episodes and may have acquired and/or genetic causes. This cross-sectional study aimed to investigate the role of methylenetetrahydrofolate reductase (MTHFR; C677T; A1298C) and cystathionine-β-synthase (CBS; T833C/844ins68, G919A) polymorphisms in serum levels of folic acid, vitamin B12 and Hcy, and to verify a possible association between these polymorphisms and the clinical variability. Blood samples of Brazilian patients with a diagnosis of thrombosis were submitted to genotyping by PCR-based methods and serum dosages of folic acid, vitamin B12 and Hcy. Except for the CBS G919A polymorphism, all other genetic markers were in Hardy-Weinberg equilibrium. An increased risk for venous thrombosis was found for the MTHFR 1298CC carriers (OR = 1.688; 95%CI = 0.839-3.398, P = 0.018) and those homozygously mutant for the CBS haplotype 844ins68/T833C (OR = 2.488; 95%CI = 0.501-12.363, P = 0.031), while heterozygous for this CBS haplotype showed an increased risk for higher Hcy levels (OR = 5.900; 95%CI = 1.003-34.691, P = 0.030). Significant interactions were observed among the MTHFR C677T, MTHFR A1298C and CBS haplotype 844ins68/T833C polymorphisms in the results for Hcy levels (P = 0.000), where heterozygous had higher values. Interactions among these polymorphisms can affect serum Hcy levels, where multiple heterozygosis could be a risk factor for vaso-occlusive episodes.
authors.affiliation: Fundação Hemocentro de Brasília, Brasília, DF, Brasil.|Núcleo de Hematologia e Hemoterapia do Hospital de Base do Distrito Federal, Brasília, DF, Brasil.
authors.forename: F M
authors.initials: FM
authors.lastname: Amaral
authors.affiliation: Instituto de Ciências Biológicas, Departamento de Genética e Morfologia, Universidade de Brasília, Brasília, DF, Brasil.
authors.forename: A L
authors.initials: AL
authors.lastname: Miranda-Vilela
authors.affiliation: Núcleo de Hematologia e Hemoterapia do Hospital de Base do Distrito Federal, Brasília, DF, Brasil.|Instituto de Ciências Biológicas, Departamento de Genética e Morfologia, Universidade de Brasília, Brasília, DF, Brasil.
authors.forename: G S
authors.initials: GS
authors.lastname: Lordelo
authors.affiliation: Instituto de Ciências Biológicas, Departamento de Genética e Morfologia, Universidade de Brasília, Brasília, DF, Brasil.|Centro Universitário Unieuro, Brasília, DF, Brasil.
authors.forename: I F
authors.initials: IF
authors.lastname: Ribeiro
authors.affiliation: Núcleo de Hematologia e Hemoterapia do Hospital de Base do Distrito Federal, Brasília, DF, Brasil.
authors.forename: M B
authors.initials: MB
authors.lastname: Daldegan
authors.affiliation: Instituto de Ciências Biológicas, Departamento de Genética e Morfologia, Universidade de Brasília, Brasília, DF, Brasil grisolia@unb.br.
authors.forename: C K
authors.initials: CK
authors.lastname: Grisolia
mesh_terms: D000293:Adolescent; D000328:Adult; D001938:Brazil; D003430:Cross-Sectional Studies; D003541:Cystathionine beta-Synthase / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005492:Folic Acid / Q000097:blood; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D019851:Thrombophilia / Q000097:blood / Q000235:genetics; D013927:Thrombosis / Q000097:blood / Q000235:genetics*; D014805:Vitamin B 12 / Q000097:blood; D055815:Young Adult
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D003541:Cystathionine beta-Synthase; D014805:Vitamin B 12