A study of the association between one carbon metabolism and blood pressure in adults and transgenerationally between pregnant women and their children
- Autores: Gemma Ornosa Martín
- Directores de la Tesis: Michelle Murphy (dir. tes.)
- Lectura: En la Universitat Rovira i Virgili ( España ) en 2019
- Idioma: español
- Tribunal Calificador de la Tesis: Joan Fernández Ballart (presid.), Carles Lerín Martínez (secret.), Mary Ward (voc.)
- Programa de doctorado: Programa de Doctorado en Biomedicina por la Universidad Rovira i Virgili
- Materias:
- Enlaces
- Tesis en acceso abierto en: TDX
- Resumen
One carbon (1C) metabolism nutrients and the MTHFR 677 C>T polymorphism have been found to be associated with blood pressure and hypertension and the mechanism associated is thought to be fetal programming. An adequate status of 1C metabolism nutrients has been proven to be beneficial for some health outcomes in adults and also in pregnancy, from in utero development until later in life including childhood and adulthood. Mandatory folic acid fortification of flour has been demonstrated to reduce the incidence of neural tube defects (NTDs) and to lower fasting plasma total homocysteine (tHcy). There is still some inconsistency in the evidence associating 1C metabolism with blood pressure and pregnancy 1C metabolism with blood pressure in the offspring.
The aim of this thesis is to explore the associations between 1C metabolism nutrients, including B-vitamins and tHcy, as well as the MTHFR 677C>T polymorphism, and blood pressure and hypertension in two different populations, an adult population and a mother-child study with follow-up during pregnancy and children at 7.5 years.
Seven hundred and eighty eight participants randomly selected from the population town halls' registers participated in the population study. This population is unexposed to mandatory folic acid fortification and B vitamin supplement use.
Both women and men in the 3rd tHcy tertile had lower folate and cobalamin status, and more of them had suboptimal riboflavin status (based on erythrocyte glutathionine reductase activation coefficient category) compared to the other tertiles. Being in the 3rd tertile of tHcy compared to the 1st increases the risk of having hypertension 1.8 times [OR=1.8 (1.0, 3.3)] in the total population. Stratifying for age, indicates that the tHcy-hypertension association is driven by that in the >50 years group [OR= 2.5 (1.2, 5.4)]. Having the MTHFR 677TT genotype increases the probability of having hypertension compared to the other genotypes, and the association is maintained after adjusting for confounding variables, in people aged ≤ 50 years [OR= 8.2 (1.3, 53.9)].
In the Reus-Tarragona Birth Cohort two hundred and twelve mother-child dyads were followed up during pregnancy and children at 7.5 years. Anthropometrical, clinical and lifestyle data was collected from pregnant women throughout pregnancy and later in the children. Biochemical data was obtained from fasting blood samples collected at <12 GW, 24-27 GW, 34 GW, labour, cord and from the children at 7.5 years. Blood pressure measurements were taken at the child check-up visit and then during 24h with Ambulatory Blood Pressure Monitoring (ABPM). Maternal and child plasma and red blood cell (RBC) folate, plasma cobalamin, fasting plasma total homocysteine (tHcy), methylmalonic acid (MMA), maternal holotranscobalamin (holoTC) and Erythrocyte Glutathione Reductase Activation assay (EGRAC) were determined from fasting blood samples as well as the MTHFR 677 C>T polymorphism. SBP and DBP mean at check-up was 104.1 and 65.1 mmHg, respectively.
No differences were observed between girls and boys. The prevalence of child hypertension was 6.2%. Looking at ABPM, mean SBP and DBP measured with ABPM was 103.2 and 61.6 mmHg, respectively. Girls’ systolic ABPM mean was lower than boys’. Diastolic ABPM mean was similar between sexes. Using multiple logistic regression analysis we observed that child CT genotype was associated with increased probability of having prehypertension or hypertension [OR=6.5 (1.0, 43.5)] in the office BP model. Maternal MTHFR 677 CT genotype was also associated with increased probability of having prehypertension or hypertension [OR= 7.4 (1.0, 55.0)].
We found that the MTHFR 677 C>T polymorphism is associated with increased risk of hypertension both in the adult population and in early life.
