000179421 001__ 179421 000179421 005__ 20240229145543.0 000179421 0247_ $$2doi$$a10.1093/jn/nxab444 000179421 0247_ $$2pmid$$apmid:34967850 000179421 0247_ $$2pmc$$apmc:PMC8971010 000179421 0247_ $$2ISSN$$a0022-3166 000179421 0247_ $$2ISSN$$a1541-6100 000179421 0247_ $$2altmetric$$aaltmetric:120063200 000179421 037__ $$aDKFZ-2022-00663 000179421 041__ $$aEnglish 000179421 082__ $$a610 000179421 1001_ $$aCheng, Ting-Yuan David$$b0 000179421 245__ $$aAssociations between Genetic Variants and Blood Biomarkers of One-Carbon Metabolism in Postmenopausal Women from the Women's Health Initiative Observational Study. 000179421 260__ $$aBethesda, Md.$$bOxford University Press$$c2022 000179421 3367_ $$2DRIVER$$aarticle 000179421 3367_ $$2DataCite$$aOutput Types/Journal article 000179421 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1649244462_24917 000179421 3367_ $$2BibTeX$$aARTICLE 000179421 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000179421 3367_ $$00$$2EndNote$$aJournal Article 000179421 520__ $$aGenetic 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.We investigated associations between genetic variants and biomarkers of one-carbon metabolism using data from the Women's Health Initiative Observational Study.In 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.After 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.Our findings on genetic variants associated with several one-carbon metabolism biomarkers may help elucidate mechanisms of maintaining B vitamin status in postmenopausal women. 000179421 536__ $$0G:(DE-HGF)POF4-313$$a313 - Krebsrisikofaktoren und Prävention (POF4-313)$$cPOF4-313$$fPOF IV$$x0 000179421 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de 000179421 650_7 $$2Other$$aMTHFR 000179421 650_7 $$2Other$$afolate 000179421 650_7 $$2Other$$aone-carbon metabolism 000179421 650_7 $$2Other$$apostmenopausal women 000179421 650_7 $$2Other$$asingle-nucleotide variants 000179421 650_7 $$2NLM Chemicals$$aBiomarkers 000179421 650_7 $$2NLM Chemicals$$aHistocompatibility Antigens 000179421 650_7 $$00LVT1QZ0BA$$2NLM Chemicals$$aHomocysteine 000179421 650_7 $$07440-44-0$$2NLM Chemicals$$aCarbon 000179421 650_7 $$0935E97BOY8$$2NLM Chemicals$$aFolic Acid 000179421 650_7 $$0EC 1.5.1.20$$2NLM Chemicals$$aMethylenetetrahydrofolate Reductase (NADPH2) 000179421 650_7 $$0EC 2.1.1.43$$2NLM Chemicals$$aEHMT2 protein, human 000179421 650_7 $$0EC 2.1.1.43$$2NLM Chemicals$$aHistone-Lysine N-Methyltransferase 000179421 650_2 $$2MeSH$$aAged 000179421 650_2 $$2MeSH$$aBiomarkers 000179421 650_2 $$2MeSH$$aCarbon: metabolism 000179421 650_2 $$2MeSH$$aFemale 000179421 650_2 $$2MeSH$$aFolic Acid 000179421 650_2 $$2MeSH$$aGenotype 000179421 650_2 $$2MeSH$$aHistocompatibility Antigens 000179421 650_2 $$2MeSH$$aHistone-Lysine N-Methyltransferase: genetics 000179421 650_2 $$2MeSH$$aHomocysteine 000179421 650_2 $$2MeSH$$aHumans 000179421 650_2 $$2MeSH$$aMethylenetetrahydrofolate Reductase (NADPH2): genetics 000179421 650_2 $$2MeSH$$aMethylenetetrahydrofolate Reductase (NADPH2): metabolism 000179421 650_2 $$2MeSH$$aMiddle Aged 000179421 650_2 $$2MeSH$$aPostmenopause: genetics 000179421 650_2 $$2MeSH$$aWomen's Health 000179421 7001_ $$aIlozumba, Mmadili N$$b1 000179421 7001_ $$0P:(DE-HGF)0$$aBalavarca, Yesilda$$b2 000179421 7001_ $$aNeuhouser, Marian L$$b3 000179421 7001_ $$aMiller, Joshua W$$b4 000179421 7001_ $$aBeresford, Shirley A A$$b5 000179421 7001_ $$00000-0002-3078-4200$$aZheng, Yingye$$b6 000179421 7001_ $$aSong, Xiaoling$$b7 000179421 7001_ $$aDuggan, David J$$b8 000179421 7001_ $$00000-0003-1079-2606$$aToriola, Adetunji T$$b9 000179421 7001_ $$aBailey, Lynn B$$b10 000179421 7001_ $$aGreen, Ralph$$b11 000179421 7001_ $$aCaudill, Marie A$$b12 000179421 7001_ $$aUlrich, Cornelia M$$b13 000179421 773__ $$0PERI:(DE-600)1469429-3$$a10.1093/jn/nxab444$$gVol. 152, no. 4, p. 1099 - 1106$$n4$$p1099 - 1106$$tThe journal of nutrition$$v152$$x0022-3166$$y2022 000179421 909CO $$ooai:inrepo02.dkfz.de:179421$$pVDB 000179421 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b2$$kDKFZ 000179421 9131_ $$0G:(DE-HGF)POF4-313$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vKrebsrisikofaktoren und Prävention$$x0 000179421 9141_ $$y2022 000179421 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2021-01-27 000179421 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2021-01-27 000179421 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2021-01-27 000179421 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2022-11-29 000179421 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2022-11-29 000179421 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2022-11-29 000179421 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2022-11-29 000179421 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2022-11-29 000179421 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2022-11-29 000179421 915__ $$0StatID:(DE-HGF)1060$$2StatID$$aDBCoverage$$bCurrent Contents - Agriculture, Biology and Environmental Sciences$$d2022-11-29 000179421 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bJ NUTR : 2021$$d2022-11-29 000179421 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2022-11-29 000179421 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2022-11-29 000179421 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5$$d2022-11-29 000179421 9201_ $$0I:(DE-He78)C120-20160331$$kC120$$lPräventive Onkologie$$x0 000179421 980__ $$ajournal 000179421 980__ $$aVDB 000179421 980__ $$aI:(DE-He78)C120-20160331 000179421 980__ $$aUNRESTRICTED