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| Author(s): |
Lana Carneiro Almeida
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Saúde Pública (FSP/CIR) |
| Defense date: | 2010-08-26 |
| Examining board members: |
Marly Augusto Cardoso;
Vania D\'Almeida;
Marcelo Macedo Rogero;
Elvira Maria Guerra Shinohara;
Nadia Maria Frizzo Trugo
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| Advisor: | Marly Augusto Cardoso |
| Abstract | |
Introduction Hyperomocysteinemia is a risk factor for neural tube defect and vascular and neurodegenerative diseases, and has genetic, metabolic and environmental determinants. Studies evaluating frequency of polymorphisms related to homocysteine (Hcy) metabolism and its relation with diet, lifestyle factors and plasma Hcy concentration in Brazilian population are scarce. Objectives To assess the frequency of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, methionine synthase reductase (MTRR) A66G and reduced folate carrier (RFC) A80G gene polymorphisms, and examine its association with dietary factors, lifestyle and serum or plasma Hcy and vitamins B12, B6 and folate among low-income Brazilian women. Subjects and methods This cross-sectional study included 609 women (21-65 years) participating in The Brazilian Investigation into Nutrition and Cervical Cancer Prevention Study (BRINCA Study), excluding cancer cases. The dietary intakes regarding the previous year were estimated using a validated food frequency questionnaire. Fasting blood samples were taken from each study participant, protected from light, immediately separated plasma or serum and storaged at -70oC. Serum folate and vitamin B12 concentrations were measured by fluoroimmunoassay, and plasma vitamin B6 and Hcy concentrations were assessed by reverse-phase high performance liquid chromatography. Gene polymorphisms were ascertained using the protein chain reaction-based method. Statistical analyses were performed using STATA 10.0, using a statistical significance level of p<0,05. Results Frequencies for the homozygous variant genotypes were: 6.6 per cent (MTHFR 677TT), 4.4 per cent (MTHFR 1298CC), 4.5 per cent (MTR 2756GG), 17.1 per cent (MTRR 66GG) and 24.4 per cent (RFC 80AA) of the analysed women. MTHFR 677TT genotype has been associated to higher plasma Hcy concentration and lower serum folate and vitamin B12 concentration, compared to 677CT and 677CC genotypes (p<0,005). On the contrary, women carrying MTHFR A1298C, MTR A2756G and MTRR A66G wild homozygous have presented higher plasma Hcy concentrations when compared to those heterozygous and/or polymorphic homozygous (p<0,005). The effect of a higher vitamin B6 consumption on plasma Hcy concentration was more pronounciated among smokers than non-smokers (interaction p=0.025). Among smokers, mean Hcy values among 677TT subjects were 64.8 per cent and 51.8 per cent higher than 677CT and 677CC, respectively; 1298CC subjects presented higher plasma Hcy concentrations than 1298AA and 1298AC; among non-smokers, however, 1298AC subjects showed lower plasma Hcy concentrations than 1298AA subjects. Smokers who reported coffee intake >173g/d had plasma Hcy concentrations 1.3 mol/L (12.7 per cent) higher than non-smokers consuming coffee 173g/d (interaction p=0.042). Non-drinkers women who reported be smokers showed median plasma Hcy concentrations 3.4 mol/L (35 per cent) higher than those with alcohol consumption >21.4g/d, but non-smokers (interaction p=0.008). Conclusion In this women sample with low prevalence of serum folate deficiency (5.1 per cent), lifestyle factors, especially smoking and alcohol consumption, modifie the relation among food intake, polymorphisms and plasma Hcy concentration, reforcing the health recommendations to stop smoking and moderate alcohol consumption (AU) | |