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000179421 041__ $$aEnglish
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000179421 1001_ $$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$$c2022
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000179421 520__ $$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.
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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
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