title: Functional polymorphisms of folate-metabolizing enzymes in relation to homocysteine concentrations in systemic lupus erythematosus.
abstract: OBJECTIVE
  To determine if functional polymorphisms of folate/homocysteine pathway enzymes are associated with homocysteine concentrations and/or coronary artery calcification (CAC) scores in patients with systemic lupus erythematosus (SLE) and controls.
  
  
  METHODS
  We investigated 163 SLE patients and 160 controls. Functional polymorphisms in 6 genes in the folate/homocysteine pathway were genotyped: 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C>T, MTHFR 1298A>C, cystathionine ss-synthase (CBS) 844ins68, methionine synthase (MTR) 2756A>G, methionine synthase reductase (MTRR) 66A>G, thymidylate synthase (TYMS) 1494del6, and dihydrofolate reductase (DHFR) c.86+60_78.
  
  
  RESULTS
  Homocysteine levels were higher in African American SLE patients than Caucasian patients and African American controls. Genotype distributions were significantly different in African American and Caucasian controls for 6 of the 7 polymorphisms. Genotype distributions for each polymorphism did not differ significantly between SLE patients and controls even after stratification by race. Glomerular filtration rate was strongly negatively correlated to homocysteine levels, and was therefore adjusted for as a covariate in the models of the effects of the polymorphisms on homocysteine levels. In SLE patients none of the 7 polymorphisms was associated with homocysteine concentrations. In Caucasian controls only MTHFR 677C>T and 1298A>C showed effects on homocysteine similar to what would be expected from the literature. There were no genotypic associations with median CAC scores in SLE patients or controls with and without stratification by race.
  
  
  CONCLUSIONS
  Polymorphisms in folate/homocysteine metabolizing enzymes do not predict higher homocysteine levels or CAC scores in patients with SLE.
authors.affiliation: Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Summers
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cucchiara
authors.forename: Eleni
authors.initials: E
authors.lastname: Nackos
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Hammons
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mohr
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Whitehead
authors.forename: Joan M
authors.initials: JM
authors.lastname: Von Feldt
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics / Q000378:metabolism; D000328:Adult; D001741:Black or African American / Q000235:genetics / Q000706:statistics & numerical data; D001213:Asian / Q000235:genetics / Q000706:statistics & numerical data; D003324:Coronary Artery Disease / Q000208:ethnology; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics / Q000378:metabolism; D005492:Folic Acid / Q000378:metabolism*; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics / Q000706:statistics & numerical data; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology* / Q000235:genetics* / Q000378:metabolism; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data
chemical_list: D004798:Enzymes; D006710:Homocysteine; D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013762:Tetrahydrofolate Dehydrogenase; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D013940:Thymidylate Synthase; D003541:Cystathionine beta-Synthase
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