Influence of PON1 polymorphisms on the association between serum paraoxonase 1 and homocysteinemia in a general population.
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Biomedical subjects
Publications and source records attributed to Michelle M Murphy.
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The aim of this study was to investigate the longitudinal changes in serum paraoxonase-1 (PON1) activity from preconception throughout normal pregnancy and their relationships with maternal dietary vitamin C and E intake. The study was performed in 35 women (studied at preconception, at 8, 20 and 32 weeks of pregnancy, and at labour). PON1 activity decreased significantly from 145.8 (109.8-198.8) U/L at preconception to 111.1 (85.3-179.9) U/L (p<0.01) at 32 weeks and 100.4 (54.7-171.4) U/L (p<0.001) at labour. There was a direct association between vitamin C intake and PON1 at week 32 (p=0.018). We conclude that adequate vitamin C intake in pregnant women may merit consideration, since vitamin C supplementation has proved beneficial in the prevention of preeclampsia in women at increased risk of this condition.
C-reactive protein (CRP) has been proposed as an independent risk factor for cardiovascular disease. In this study we sought to investigate the association between several nutritional and lifestyle factors and serum CRP concentration in a population-based study. We studied 359 individuals (172 women, 187 men; age range 18-75 years) randomly selected from the town hall's registers and assessed their daily dietary intake using a 3-day estimated-food record. The median serum CRP concentration was 1.40 mg/L (range <0.10-47.48 mg/L; geometric mean 1.20 mg/L). We noted significant and independent direct associations between CRP and age, body-mass index, female sex, and serum triglyceride concentration. Bivariate analysis showed a significant inverse association between CRP and many nutrients (e.g., carbohydrates, proteins, lipids, thiamine, pyridoxine, tocopherol, and folate), but multiple-regression analysis indicated that only the effect of dietary folate intake was not dependent on other factors. Differences in folate intake did not produce changes in plasma homocysteine concentration, and we detected no negative correlation between dietary folate intake and log homocysteine (r = .02, P = .711). Strong positive correlations between the intake of folate and numerous other nutrients were found. This population-based study shows that a higher folate intake, in addition to other known constitutive and lifestyle factors, is significantly associated with a lower serum CRP concentration.
C-Reactive protein has been associated with several complications of pregnancy. The aims of the present study were: (1) to evaluate a turbidimetric immunoassay for the measurement of C-reactive protein; and (2) to investigate the chronological changes of the levels of this protein from preconception throughout normal pregnancy and its relationship with variables associated with preconception and pregnancy outcome. Inter-assay imprecision was <5% for C-reactive protein >1 mg/L and 18% at a mean value of 0.33 mg/L. The limit of detection was 0.10 mg/L. The method was linear between 0.10 and 30 mg/L. There were no observed interferences from jaundice, hemolysis, lipemia or paraproteinemia at the levels studied. There was good agreement with the nephelometric method. A total of 39 women were studied at preconception, at 8, 20 and 32 weeks of pregnancy, and in labor. Preconception C-reactive protein concentration was 1.17+/-0.18 mg/L and increased (p<0.001) throughout pregnancy up to 5.69+/-0.82 mg/L. Body mass index at preconception and weight gain during pregnancy were the main factors associated with this increase in C-reactive protein.
BACKGROUND: Increased homocysteine has been associated with pregnancy complications. METHODS: We investigated prospectively the effect of maternal homocysteine on normal pregnancy outcome. The study included 93 women and their offspring; 39 of the women took folic acid during the second and/or third trimesters of pregnancy. We measured homocysteine at preconception; at weeks 8, 20, and 32 of pregnancy; during labor; and in the fetal cord; we also recorded birth weight. RESULTS: Geometric mean (SE) maternal total homocysteine (tHcy) increased between 32 weeks of pregnancy and labor [7.98 (1.05) micromol/L in unsupplemented women and 6.26 (1.07) micromol/L in supplemented women; P <0.0001 for both]. Fetal tHcy was lower than maternal tHcy [6.39 (1.06) micromol/L in unsupplemented pregnancies (P <0.0001), and 5.18 (1.06) micromol/L in supplemented pregnancies (P <0.05)]. Maternal tHcy was correlated from preconception throughout pregnancy (8 weeks, r = 0.708; 20 weeks, r = 0.637; 32 weeks, r = 0.537; labor, r = 0.502; P <0.0001 for all time points) and with fetal tHcy [preconception, r = 0.255 (P <0.05); 8 weeks, r = 0.321 (P <0.01); 20 weeks, r = 0.469; 32 weeks, r = 0.550; labor, r = 0.624 (P <0.0001)]. Mothers in the highest tHcy tertile at 8 weeks of pregnancy were three times [odds ratio, 3.26 (95% confidence interval, 1.05-10.13); P <0.05] and at labor were four times [3.65 (1.15-11.56); P <0.05] more likely to give birth to a neonate in the lowest birth weight tertile. Neonates of mothers in the highest tHcy tertile at labor weighed, on average, 227.98 g less than those of mothers in the low and medium tertiles (P = 0.014). CONCLUSIONS: Supplemented mothers had lower tHcy at labor than unsupplemented mothers, as did their neonates. Maternal and fetal tHcy was significantly correlated throughout the study. Neonates of mothers in the highest tertile of homocysteine weighed less.
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BACKGROUND: Paraoxonase may protect lipoproteins and cell membranes from peroxidation, and alterations in the activity of this enzyme have been associated with some chronic diseases. Serum paraoxonase appears to be mainly under genetic control, but some studies suggest that environmental factors may also modulate its activity. The aim of the present study was to investigate whether diet and lifestyle affect serum paraoxonase activity. METHODS: We studied a population-based sample of 388 individuals (194 women and 194 men; age range, 18-75 years) and assessed their daily dietary intake using a 3-day estimated food record. The variables studied included serum paraoxonase activity, paraoxonase polymorphisms at positions 55 and 192, age, gender, smoking status, physical exercise, body mass index, energy consumption, nutrient intake (total lipids, saturated fatty acids, beta-carotenes, vitamins C and E), and serum lipid concentrations. RESULTS: Multiple linear regression analysis showed that only genetic polymorphisms, serum cholesterol, HDL-cholesterol concentrations, and cigarette smoking were significant predictors of serum paraoxonase activity. HDL-cholesterol concentrations were also related to body mass index, daily energy consumption, and saturated fatty acid intake. CONCLUSIONS: The between-individual variability of serum paraoxonase activity is regulated mainly by genetic determinants. Although HDL-cholesterol and tobacco smoking may contribute to the modulation of this enzyme, the other nutritional and lifestyle factors do not seem to play a significant role.
OBJECTIVES: This study measured the response of deoxypyridinoline, a biomarker of bone resorption, during 11 weeks of Marine recruit training. METHODS: Urine samples were obtained from 155 female and 58 male Marine recruits from the first morning void every 3 days during training. Training miles of weight-bearing exercise were recorded daily, and injury data were obtained from the medical clinic staff. RESULTS: Deoxypyridinoline was significantly (p < 0.001) increased at week 2 and weeks 9 through 11 for women and at weeks 10 and 11 for men. The increase in bone resorption corresponded to an increase in miles of weight-bearing exercise performed throughout training. The incidence of stress fracture and reaction was 3.9% and 14.8%, respectively, for women and 1.7% and 3.4%, respectively, for men. CONCLUSIONS: Significant bone resorption took place at the end of Marine recruit training due to accumulation of weight-bearing exercise throughout training and the increase in marching toward the end.
BACKGROUND: Fasting plasma total homocysteine (tHcy) decreases during pregnancy. Previous reports suggested that this is due to folic acid supplementation, hemodilution, or a decrease in albumin. However, these hypotheses have not been tested in a longitudinal study. OBJECTIVE: We investigated the relation between pregnancy-related physiologic changes and tHcy in a group of healthy women who were either unsupplemented or supplemented with folic acid. DESIGN: In a longitudinal study from preconception throughout pregnancy, we studied 54 unsupplemented women and 39 women who were supplemented with folic acid during the second or third trimester of pregnancy. tHcy, hematocrit, and serum albumin were determined preconceptionally and at 8, 20, and 32 wk of pregnancy. RESULTS: For the entire group, geometric mean tHcy concentrations at preconception (8.2 micro mol/L) were significantly greater (P < 0.001) than those at 8 wk of pregnancy (6.4 micro mol/L). When the unsupplemented and supplemented groups were regarded separately, geometric mean tHcy concentrations at preconception were significantly greater than those at 20 (5.22 and 4.18 micro mol/L, respectively) and 32 (5.16 and 4.42 micro mol/L, respectively) wk of pregnancy (P < 0.001 for both). Mean reductions from preconception concentrations at 8, 20, and 32 wk of pregnancy were significantly greater (P < 0.001) for tHcy (-11.5%, -25.5%, and -24.5%, respectively) than for hematocrit (-1.9%, -4.2%, and -4.3%, respectively) or serum albumin (-1.1%, -9.8%, and -13.4%, respectively). There was no correlation between changes in either hematocrit or serum albumin and changes in tHcy. CONCLUSIONS: This study refutes the previous explanations for the reduction in plasma tHcy known to occur in pregnancy, namely, folic acid supplementation, hemodilution, and a decrease in serum albumin. We suggest that the changes may be endocrine-based.
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