Evidence map›Paper›PMID 34967850›Full record

Observational studyThe Journal of nutrition2022

Associations between Genetic Variants and Blood Biomarkers of One-Carbon Metabolism in Postmenopausal Women from the Women's Health Initiative Observational Study.

Ting-Yuan David Cheng, Mmadili N Ilozumba, Yesilda Balavarca, Marian L Neuhouser, Joshua W Miller, Shirley A A Beresford, Yingye Zheng, Xiaoling Song, David J Duggan, Adetunji T Toriola and 4 more

Registry-linked trialOpen access · greenAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in The Journal of nutrition, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02328677 (ColoCare Transdisciplinary Research in Colorectal Cancer Prognosis), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 36% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02328677 recruitingnot on this map

ColoCare Transdisciplinary Research in Colorectal Cancer Prognosis

TypeobservationalSponsorUniversity of UtahRan2007 to 2030Enrolled5,000ConditionsColorectal Cancer
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Common Variants in One-Carbon Metabolism Genes (International journal of molecular sciences · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 10 institutions in 2 countries.

Ting-Yuan David ChengDepartment of Epidemiology, University of Florida, Gainesville, FL, USA.
Mmadili N IlozumbaDepartment of Epidemiology, University of Florida, Gainesville, FL, USA.
Yesilda BalavarcaDepartment of Preventive Oncology, National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany.
Marian L NeuhouserPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Joshua W MillerDepartment of Nutritional Sciences, Rutgers University, New Brunswick, NJ, USA.
Shirley A A BeresfordPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Yingye ZhengPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.ORCID 0000-0002-3078-4200
Xiaoling SongPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
David J DugganTranslational Genomics Research Institute, Phoenix, AZ, USA.
Adetunji T ToriolaDepartment of Surgery, Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0003-1079-2606
Lynn B BaileyDepartment of Foods and Nutrition, University of Georgia, Athens, GA, USA.
Ralph GreenDepartment of Pathology and Laboratory Medicine, University of California Davis, Davis, CA, USA.
Marie A CaudillDivision of Nutritional Sciences, Cornell University, Ithaca, NY, USA.
Cornelia M UlrichHuntsman Cancer Institute, Salt Lake City, UT, USA.
Fred Hutch Cancer Center · USUniversity of Florida · USCornell University · USNational Center for Tumor Diseases · DERutgers, The State University of New Jersey · USTranslational Genomics Research Institute · USUniversity of California, Davis · USUniversity of Georgia · USUniversity of Utah · USWashington University in St. Louis · US

Funding

Translational Research Support CoreP30ES005022 · NIEHS · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI Jose Guillermo Cedeno Laurent · 1988 to 2026
$47.4M
A Prospective Study of Colorectal Cancer: One-Carbon Metabolism and InflammationR01CA120523 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ULRICH, CORNELIA M · 2008 to 2012
$3.0M
WOMENS HEALTH INITIATIVE-N01WH22110N01WH022110 · WH · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ROSS, PRENTICE · 1992 to 2006
$1.2M
mTOR pathway in breast cancer subtypes by race: A molecular pathological studyK07CA201334 · NCI · UNIVERSITY OF FLORIDA · PI CHENG, TING-YUAN · 2016 to 2020
$693k
NCI NIH HHS K07 CA201334NCI NIH HHS R01 CA120523NHLBI NIH HHS HHSN268201100001INHLBI NIH HHS HHSN268201100002INHLBI NIH HHS HHSN268201100003INHLBI NIH HHS HHSN268201100004INHLBI NIH HHS HHSN268201100046CNIA NIH HHS HHSN271201100004CNIEHS NIH HHS P30 ES005022NIH HHS R01 CA120523WHI NIH HHS HHSN268201100001CWHI NIH HHS HHSN268201100002CWHI NIH HHS HHSN268201100003CWHI NIH HHS HHSN268201100004CWHI NIH HHS N01 WH022110
6 · The paper itself

Abstract

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.

Indexed as

Methylenetetrahydrofolate Reductase (NADPH2)PostmenopauseAgedBiomarkersCarbonFemaleFolic AcidGenotypeHistocompatibility AntigensHistone-Lysine N-MethyltransferaseHomocysteineHumansMiddle AgedWomen's HealthBiomarkersCarbonEHMT2 protein, humanFolic AcidHistocompatibility AntigensHistone-Lysine N-MethyltransferaseHomocysteineMethylenetetrahydrofolate Reductase (NADPH2)folateMTHFRone-carbon metabolismpostmenopausal womensingle-nucleotide variants

Identifiers

PMID34967850
PMCPMC8971010
OpenAlexW4205308194

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.