title: Association of methylenetetrahydrofolate (MTHFR) and apolipoprotein E (apo E) genotypes with homocysteine, vitamin and lipid levels in carotid stenosis.
abstract: The aim of the study was to investigate the association between methylenetetrahydrofolate (MTHFR) genotypes and levels of homocysteine (Hcy), folate, vitamin B12 and lipids as well as the association between apolipoprotein E (apo E) genotypes and levels of lipids in a Croatian healthy control group and a group of patients with > 70% carotid stenosis (CS). The study included 98 Croats, 38 patients with > 70% carotid stenosis and 60 age- and sex-matched controls. The MTHFR and apo E genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), Hcy by enzyme immunoassay, vitamins by immunochemiluminiscence, and lipids by spectrophotometric method. There was no difference between control subjects and CS patients in the distribution of C677T MTHFR genotypes (p=0. 786) and alleles (p=0.904), however, differences in the frequencies of apo E genotypes (p=0.012) and alleles (p=0.029) were statistically significant. The odds ratio for apo E 3/4 genotype was 3.93 (95% CI 1.23-12.61). Hyperhomocysteinemia (> or =15 micromol/L) was found in 11% of CS patients and 5% of control subjects. Total cholesterol, triglycerides, vitamin B12 and folate were statistically different in "all MTHFR genotypes" (p<0.001, p<0.01, p=0.044 and p=0.036, respectively), and in TC/TT (p<0.001, p=0.003, p=0.030 and p=0.032, respectively) groups. The levels of total cholesterol, LDL cholesterol and triglycerides in the apo E 3/3, and total cholesterol in the apo E 3/4 group yielded statistical difference. An association was found of apo E 3/4 genotype but not of MTHFR genotypes with the risk of CS. MTHFR and apo E affect blood lipid levels, which was statistically confirmed. An association was also recorded between hyperhomocysteinemia and patients with CS. Vitamin status in CS showed a statistically verified association with TC/TT MTHFR genotype. In the group of patients with TC/TT MTHFR genotype, lower vitamin B12 and higher folate values were recorded. The results of multiple logistic analysis showed that there was no statistical significance of Hcy levels (OR 2.403, p=0.334) or conventional vascular risk factors such as smoking habit (OR 0.505, p=0.149), age (OR 1.048, p=0.087) or sex (OR 2.037, p=0.112) in predicting CS.
authors.affiliation: Department of Analytical Toxicology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia. izuntar@pharma.hr
authors.forename: Irena
authors.initials: I
authors.lastname: Zuntar
authors.forename: Natasa
authors.initials: N
authors.lastname: Antoljak
authors.forename: Nada
authors.initials: N
authors.lastname: Vrkić
authors.forename: Elizabeta
authors.initials: E
authors.lastname: Topić
authors.forename: Nikola
authors.initials: N
authors.lastname: Kujundzić
authors.forename: Vida
authors.initials: V
authors.lastname: Demarin
authors.forename: Vlasta
authors.initials: V
authors.lastname: Vuković
mesh_terms: D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2) / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D016893:Carotid Stenosis / Q000097:blood / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005787:Gene Frequency; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D014805:Vitamin B 12 / Q000097:blood*
chemical_list: D001057:Apolipoproteins E; D006710:Homocysteine; D005492:Folic Acid; D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D014805:Vitamin B 12