title: Associations of plasma homocysteine and the methylenetetrahydrofolate reductase C677T polymorphism with carotid intima media thickness among South Asian, Chinese and European Canadians.
abstract: BACKGROUND
  Few studies have evaluated the associations of plasma homocysteine concentration, the methylenetetrahydrofolate reductase (MTHFR) C677T genotype and B vitamin concentration with intima media thickness (IMT) in multiethnic populations.
  
  
  METHODS
  In the Study of Health Assessment and Risk in Ethnic groups (SHARE), we measured carotid IMT, fasting serum folate, serum B12, plasma pyridoxal-5'-phosphate (PLP) and plasma homocysteine and determined the MTHFR C677T genotype in a cross-sectional study of 818 South Asian, Chinese and European Canadians without previous history of CVD, cancer or diabetes during 1996-1998.
  
  
  RESULTS
  Plasma homocysteine was inversely related to serum folate, serum B12, plasma PLP, B vitamin supplement use and Chinese ethnicity, and was positively associated with hypertension, smoking, IMT, MTHFR 677T/T genotype and South Asian ethnicity. Although ethnicity was not a statistically significant modifier, among carriers of the MTHFR 677T/T genotype with serum folate < or =14 nmol/L compared to >14 nmol/L, plasma homocysteine was significantly higher among South Asians (50.9% increase, P < 0.001) and Europeans (52.4% increase, P < 0.001) but not Chinese (11.0% increase, P > 0.05). Plasma homocysteine > 11.7 micromol/L was associated with a 5.9% (95% CI: 1.9%, 10.0%) increase in IMT (approximately 0.04 mm) in the pooled-data analyses with similar increases noted in the ethnic-specific analyses. The 677T/T genotype was not associated with a significant change in IMT in the pooled-data analyses (2.7%; 95% CI: -1.7%, 7.2%) nor in ethnic-specific analyses compared to other genotypes, although there were only 63 677T/T homozygotes.
  
  
  CONCLUSIONS
  The combination of lower serum folate and the MTHFR 677T/T genotype is associated with increased plasma homocysteine among South Asians and Europeans, but the association is not evident among Chinese possibly because their serum folate may not have been low enough to compromise MTHFR activity. Plasma homocysteine > 11.7 micromol/L appears to be associated with a clinically important increase in IMT.
authors.affiliation: Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, USA. Lkelemen@post.harvard.edu
authors.forename: Linda E
authors.initials: LE
authors.lastname: Kelemen
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Anand
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.forename: Bernard
authors.initials: B
authors.lastname: Rosner
authors.forename: Walter C
authors.initials: WC
authors.lastname: Willett
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Montague
authors.forename: Eva
authors.initials: E
authors.lastname: Lonn
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vuksan
authors.forename: Koon K
authors.initials: KK
authors.lastname: Teo
authors.forename: Sudarshan
authors.initials: S
authors.lastname: Devanesen
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
mesh_terms: D001210:Asia, Southeastern / Q000208:ethnology; D002170:Canada; D002339:Carotid Arteries / Q000033:anatomy & histology*; D002681:China / Q000208:ethnology; D003430:Cross-Sectional Studies; D005006:Ethnicity; D005260:Female; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000494:pharmacology*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012016:Reference Values; D012307:Risk Factors; D017539:Tunica Intima / Q000033:anatomy & histology*
chemical_list: D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)