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Biomarkers of one-carbon metabolism are associated with biomarkers of inflammation in women.

ABSTRACT: Folate-mediated one-carbon metabolism is essential for DNA synthesis, repair, and methylation. Perturbations in one-carbon metabolism have been implicated in increased risk of some cancers and may also affect inflammatory processes. We investigated these interrelated pathways to understand their relation. The objective was to explore associations between inflammation and biomarkers of nutritional status and one-carbon metabolism. In a cross-sectional study in 1976 women selected from the Women's Health Initiative Observational Study, plasma vitamin B-6 [pyridoxal-5'-phosphate (PLP)], plasma vitamin B-12, plasma folate, and RBC folate were measured as nutritional biomarkers; serum C-reactive protein (CRP) and serum amyloid A (SAA) were measured as biomarkers of inflammation; and homocysteine and cysteine were measured as integrated biomarkers of one-carbon metabolism. Student's t, chi-square, and Spearman rank correlations, along with multiple linear regressions, were used to explore relations between biomarkers; additionally, we tested stratification by folic acid fortification period and multivitamin use. With the use of univariate analysis, plasma PLP was the only nutritional biomarker that was modestly significantly correlated with serum CRP and SAA (? = -0.22 and -0.12, respectively; P < 0.0001). Homocysteine (?mol/L) showed significant inverse correlations with all nutritional biomarkers (ranging from ? = -0.30 to ? = -0.46; all P < 0.0001). With the use of multiple linear regression, plasma PLP, RBC folate, homocysteine, and cysteine were identified as independent predictors of CRP; and PLP, vitamin B-12, RBC folate, and homocysteine were identified as predictors of SAA. When stratified by folic acid fortification period, nutrition-homocysteine correlations were generally weaker in the postfortification period, whereas associations between plasma PLP and serum CRP increased. Biomarkers of inflammation are associated with PLP, RBC folate, and homocysteine in women. The connection between the pathways needs to be further investigated and causality established. The trial is registered at clinicaltrials.gov as NCT00000611.

SUBMITTER: Abbenhardt C

PROVIDER: S-EPMC3985828 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Biomarkers of one-carbon metabolism are associated with biomarkers of inflammation in women.

Abbenhardt Clare C Miller Joshua W JW Song Xiaoling X Brown Elissa C EC Cheng Ting-Yuan David TY Wener Mark H MH Zheng Yingye Y Toriola Adetunji T AT Neuhouser Marian L ML Beresford Shirley A A SA Makar Karen W KW Bailey Lynn B LB Maneval David R DR Green Ralph R Manson Joann E JE Van Horn Linda L Ulrich Cornelia M CM

The Journal of nutrition 20140319 5

Folate-mediated one-carbon metabolism is essential for DNA synthesis, repair, and methylation. Perturbations in one-carbon metabolism have been implicated in increased risk of some cancers and may also affect inflammatory processes. We investigated these interrelated pathways to understand their relation. The objective was to explore associations between inflammation and biomarkers of nutritional status and one-carbon metabolism. In a cross-sectional study in 1976 women selected from the Women's ...[more]

PMID: 24647390

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Project description:BackgroundGenetic variation in one-carbon metabolism may affect nutrient concentrations and biological functions. However, data on genetic variants associated with blood biomarkers of one-carbon metabolism in US postmenopausal women are limited, and whether these associations were affected by the nationwide folic acid (FA) fortification program is unclear.ObjectivesWe investigated associations between genetic variants and biomarkers of one-carbon metabolism using data from the Women's Health Initiative Observational Study.MethodsIn 1573 non-Hispanic White (NHW) and 282 Black/African American, American Indian/Alaska Native, Asian/Pacific Islander, and Hispanic/Latino women aged 50-79 y, 288 nonsynonymous and tagging single-nucleotide variants (SNVs) were genotyped. RBC folate, plasma folate, pyridoxal-5'-phosphate (PLP), vitamin B-12, homocysteine, and cysteine concentrations were determined in 12-h fasting blood. Multivariable linear regression tested associations per variant allele and for an aggregated genetic risk score. Effect modifications before, during, and after nationwide FA fortification were examined.ResultsAfter correction for multiple comparisons, among NHW women, 5,10-methylenetetrahydrofolate reductase (MTHFR) rs1801133 (677C→T) variant T was associated with lower plasma folate (-13.0%; 95% CI: -17.3%, -8.6%) and higher plasma homocysteine (3.5%; 95% CI: 1.7%, 5.3%) concentrations. Other associations for nonsynonymous SNVs included DNMT3A rs11695471 (T→A) with plasma PLP; EHMT2 rs535586 (G→A), TCN2 rs1131603 (L349S A→G), and TCN2 rs35838082 (R188W G→A) with plasma vitamin B-12; CBS rs2851391 (G→A) with plasma homocysteine; and MTHFD1 rs2236224 (G→A) and rs2236225 (R653Q G→A) with plasma cysteine. The influence of FA fortification on the associations was limited. Highest compared with lowest quartiles of aggregated genetic risk scores from SNVs in MTHFR and MTRR were associated with 14.8% to 18.9% lower RBC folate concentrations. Gene-biomarker associations were similar in women of other races/ethnicities.ConclusionsOur findings on genetic variants associated with several one-carbon metabolism biomarkers may help elucidate mechanisms of maintaining B vitamin status in postmenopausal women.

Project description:ObjectivesAlthough the biological rationale for the association between folate, vitamin B12, and homocysteine with cognitive function seems plausible, conflicting results have been reported. This study aimed to determine the associations between 1-carbon (1-C) metabolism biomarkers (folate, vitamin B12, and homocysteine), and cognitive impairment at baseline and the rate of cognitive decline over 5 years in the very old.DesignThe Newcastle 85+ Study was a prospective longitudinal study of people 85 years old and followed over 5 years in Northeast England.SettingCommunity-dwelling and institutionalized.ParticipantsThe analytical sample included 765 very old participants with 1-C metabolism biomarkers and cognitive measures.MeasurementsGlobal cognition was measured by the Standardized Mini-Mental State Examination (SMMSE) at baseline, and at 3 and 5 years of follow-up and, attention-specific cognition with the Cognitive Drug Research (CDR) System at baseline, and at 1.5 and 3.0 years of follow-up. Baseline red blood cell folate (RBC folate), plasma vitamin B12, and total homocysteine (tHcy) concentrations were determined by immunoassay. Linear mixed models were used to estimate the associations between quartiles of 1-C metabolism biomarkers and cognition over 3 (CDR) and 5 years (SMMSE).ResultsCompared with participants in the lowest quartile of RBC folate concentrations (<612 nmol/L), those in the highest quartile of RBC folate concentrations (>1280 nmol/L) had 1 more point on the SMMSE at baseline (β = +1.02, SE = 0.43, P = .02). Those in quartile 4 of tHcy (>21.4 μmol/L) had 1 point less in the SMMSE at baseline than those in the lowest quartile (<13.5 μmol/L) (β = -1.05, SE = 0.46, P = .02). Plasma vitamin B12 was not predictive of global or attention-specific cognition at baseline and at follow-up. None of the 1-C metabolism biomarkers except tHcy was associated with the rate of decline in attention scores over 3 years.ConclusionRBC folate and tHcy, but not plasma vitamin B12, were associated with better global cognition in the very old at baseline but were not predictive of rate of decline over 5 years.

Project description:BackgroundGreater red meat intake is associated with an increased type 2 diabetes and cardiovascular disease risk. However, the relation of red meat intake to biomarkers of inflammation and glucose metabolism has not been investigated thoroughly.ObjectiveWe hypothesized that greater red meat intake would be associated with biomarkers of inflammation and glucose metabolism, which would be partly explained by body mass index (BMI).DesignWe analyzed cross-sectional data from diabetes-free female participants in the Nurses' Health Study (n = 3690). Multiple linear regression was conducted to assess the associations of total, unprocessed, and processed red meat intakes (quartile categories) with plasma C-reactive protein (CRP), ferritin, adiponectin, fasting insulin, and hemoglobin A1c (Hb A1c).ResultsGreater total, unprocessed, and processed red meat intakes were associated with higher plasma CRP, ferritin, fasting insulin, and Hb A1c and lower adiponectin after adjustment for demographic information (P-trend ≤ 0.03 for all). Adiponectin was not associated with any type of red meat intake when further adjusted for medical and lifestyle factors. After adjustment for BMI, most of these associations with inflammatory and glucose metabolic biomarkers were substantially attenuated and no longer significant. BMI accounted for a statistically significant proportion of associations with CRP, Hb A1c, and fasting insulin (P-contribution ≤ 0.02 for all) but not with ferritin. Substituting a serving of total red meat intake with alternative protein food in a combination of poultry, fish, legumes, and nuts was associated with significantly lower CRP (β ± SE: -0.106 ± 0.043), ferritin (-0.212 ± 0.075), Hb A1c (-0.052 ± 0.015), and fasting insulin (-0.119 ± 0.036) (all P ≤ 0.02 for comparison of extreme quartiles for all).ConclusionsGreater red meat intake is associated with unfavorable plasma concentrations of inflammatory and glucose metabolic biomarkers in diabetes-free women. BMI accounts for a significant proportion of the associations with these biomarkers, except for ferritin. Substituting red meat with another protein food is associated with a healthier biomarker profile of inflammatory and glucose metabolism.

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Biomarkers of one-carbon metabolism are associated with biomarkers of inflammation in women.

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Biomarkers of one-carbon metabolism are associated with biomarkers of inflammation in women.

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