Plasma folate levels are associated with the lipoprotein profile: a retrospective database analysis

Semmler, Alexander; Moskau, Susanna; Grigull, Andreas; Farmand, Susan; Klockgether, Thomas; Smulders, Yvo M.; Blom, Henk J.; Zur, Bernd; Stoffel‐Wagner, Birgit; Linnebank, Michael

doi:10.1186/1475-2891-9-31

Cited by 25 publications

(28 citation statements)

References 15 publications

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“…Folate 48 and vitamin D 49 have previously been associated with higher HDL-C. Fish, a source of cardioprotective omega-3 fatty acids, are also a large source of mercury; 50 however, we did not observe a large change in effect size of mercury when accounting for consumption of fish.…”

Section: Discussioncontrasting

confidence: 69%

Systematic evaluation of environmental factors: persistent pollutants and nutrients correlated with serum lipid levels

Patel

Cullen

Ioannidis

et al. 2012

International Journal of Epidemiology

128

129

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Background Both genetic and environmental factors contribute to triglyceride, low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C) levels. Although genome-wide association studies are currently testing the genetic factors systematically, testing and reporting one or a few factors at a time can lead to fragmented literature for environmental chemical factors. We screened for correlation between environmental factors and lipid levels, utilizing four independent surveys with information on 188 environmental factors from the Centers of Disease Control, National Health and Nutrition Examination Survey, collected between 1999 and 2006. Methods We used linear regression to correlate each environmental chemical factor to triglycerides, LDL-C and HDL-C adjusting for age, age 2 , sex, ethnicity, socio-economic status and body mass index. Final estimates were adjusted for waist circumference, diabetes status, blood pressure and survey. Multiple comparisons were controlled for by estimating the false discovery rate and significant findings were tentatively validated in an independent survey. Results We identified and validated 29, 9 and 17 environmental factors correlated with triglycerides, LDL-C and HDL-C levels, respectively. Findings include hydrocarbons and nicotine associated with lower HDL-C and vitamin E (γ-tocopherol) associated with unfavourable lipid levels. Higher triglycerides and lower HDL-C were correlated with higher levels of fat-soluble contaminants (e.g. polychlorinated biphenyls and dibenzofurans). Nutrients and vitamin markers (e.g. vitamins B, D and carotenes), were associated with favourable triglyceride and HDL-C levels. Conclusions Our systematic association study has enabled us to postulate about broad environmental correlation to lipid levels. Although subject to confounding and reverse causality bias, these findings merit evaluation in additional cohorts.

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Section: Discussioncontrasting

confidence: 69%

Systematic evaluation of environmental factors: persistent pollutants and nutrients correlated with serum lipid levels

Patel

Cullen

Ioannidis

et al. 2012

International Journal of Epidemiology

128

129

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“…In cases of higher plasma folate, choline is probably spared and utilized for phospholipid synthesis. This can explain results on the inverse association between plasma folate and plasma lipoproteins (LDL-cholesterol) [64], or the increased high-density lipoprotein (HDL)-cholesterol levels after folic acid supplementation [65]. …”

Section: Metabolic Burden: Osmotic Stress and Energy Metabolismmentioning

confidence: 99%

The Metabolic Burden of Methyl Donor Deficiency with Focus on the Betaine Homocysteine Methyltransferase Pathway

2013

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Methyl groups are important for numerous cellular functions such as DNA methylation, phosphatidylcholine synthesis, and protein synthesis. The methyl group can directly be delivered by dietary methyl donors, including methionine, folate, betaine, and choline. The liver and the muscles appear to be the major organs for methyl group metabolism. Choline can be synthesized from phosphatidylcholine via the cytidine-diphosphate (CDP) pathway. Low dietary choline loweres methionine formation and causes a marked increase in S-adenosylmethionine utilization in the liver. The link between choline, betaine, and energy metabolism in humans indicates novel functions for these nutrients. This function appears to goes beyond the role of the nutrients in gene methylation and epigenetic control. Studies that simulated methyl-deficient diets reported disturbances in energy metabolism and protein synthesis in the liver, fatty liver, or muscle disorders. Changes in plasma concentrations of total homocysteine (tHcy) reflect one aspect of the metabolic consequences of methyl group deficiency or nutrient supplementations. Folic acid supplementation spares betaine as a methyl donor. Betaine is a significant determinant of plasma tHcy, particularly in case of folate deficiency, methionine load, or alcohol consumption. Betaine supplementation has a lowering effect on post-methionine load tHcy. Hypomethylation and tHcy elevation can be attenuated when choline or betaine is available.

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“…These associations were independent of gender or age, though influences of medications, diseases, physical exercise, diet, or BMI were not accounted for in that study. Interestingly, vitamin B12 was not associated with the lipoprotein profile in that reported study [19]. Cholesterol may be important for facilitating the import of folate by clustering membrane-bound folate receptors in the cell membrane [19].…”

Section: Discussionmentioning

confidence: 93%

“…Interestingly, vitamin B12 was not associated with the lipoprotein profile in that reported study [19]. Cholesterol may be important for facilitating the import of folate by clustering membrane-bound folate receptors in the cell membrane [19]. Use of clustering membrane-bound folate receptors was favoured when folate status was low [20].…”

Section: Discussionmentioning

confidence: 99%

“…Folate status is inversely associated with obesity [21], likely due to increased activity of COMT (catechol O- methyltransferase), which uses folate for methyl transfer for metabolism of catechol estrogen produced by adipose tissue. Both obesity [21] and low folate status [19] have been associated with reduced HDL cholesterol levels. However, in a recent study examining folate placental transport in obese women, it was determined that while protein expression of folate receptor-α and RFC were altered (PCFT was unchanged), the activities of the transporters was unaltered in obesity and fetal folate serum concentration were not adversely affected [22].…”

Section: Discussionmentioning

confidence: 99%

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Single nucleotide polymorphisms in CETP, SLC46A1, SLC19A1, CD36, BCMO1, APOA5, and ABCA1 are significant predictors of plasma HDL in healthy adults

et al. 2013

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BackgroundIn a marker-trait association study we estimated the statistical significance of 65 single nucleotide polymorphisms (SNP) in 23 candidate genes on HDL levels of two independent Caucasian populations. Each population consisted of men and women and their HDL levels were adjusted for gender and body weight. We used a linear regression model. Selected genes corresponded to folate metabolism, vitamins B-12, A, and E, and cholesterol pathways or lipid metabolism.MethodsExtracted DNA from both the Sacramento and Beltsville populations was analyzed using an allele discrimination assay with a MALDI-TOF mass spectrometry platform. The adjusted phenotype, y, was HDL levels adjusted for gender and body weight only statistical analyses were performed using the genotype association and regression modules from the SNP Variation Suite v7.ResultsStatistically significant SNP (where P values were adjusted for false discovery rate) included: CETP (rs7499892 and rs5882); SLC46A1 (rs37514694; rs739439); SLC19A1 (rs3788199); CD36 (rs3211956); BCMO1 (rs6564851), APOA5 (rs662799), and ABCA1 (rs4149267). Many prior association trends of the SNP with HDL were replicated in our cross-validation study. Significantly, the association of SNP in folate transporters (SLC46A1 rs37514694 and rs739439; SLC19A1 rs3788199) with HDL was identified in our study.ConclusionsGiven recent literature on the role of niacin in the biogenesis of HDL, focus on status and metabolism of B-vitamins and metabolites of eccentric cleavage of β-carotene with lipid metabolism is exciting for future study.

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Plasma folate levels are associated with the lipoprotein profile: a retrospective database analysis

Cited by 25 publications

References 15 publications

Systematic evaluation of environmental factors: persistent pollutants and nutrients correlated with serum lipid levels

Systematic evaluation of environmental factors: persistent pollutants and nutrients correlated with serum lipid levels

The Metabolic Burden of Methyl Donor Deficiency with Focus on the Betaine Homocysteine Methyltransferase Pathway

Single nucleotide polymorphisms in CETP, SLC46A1, SLC19A1, CD36, BCMO1, APOA5, and ABCA1 are significant predictors of plasma HDL in healthy adults

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