title: Methylenetetrahydrofolate reductase C677T polymorphism, hypertension and risk of stroke: a prospective, nested case-control study.
abstract: BACKGROUND
  Hyperhomocysteinemia is a risk factor for cardiovascular disease. To date, limited prospective studies have examined the joint effects of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, hyperhomocysteinemia and conventional vascular risk factors on risk of stroke and stroke death.
  
  
  METHODS
  A total of 39 165 subjects from nine communities within Anqing, Anhui Province, China were prospectively followed from March 1995 to April 2005, with an average follow-up period of 6.2 years. None of the subjects had any history of vascular events at baseline. At follow-up, 251 incident stroke cases were identified. Using a nested, case-control study design, this analysis includes 106 cases with complete MTHFR C677T genotyping data and plasma samples. We selected 106 controls without vascular events matched for age, sex, community and years of plasma storage. Plasma total homocysteine (tHcy) level was measured by high-performance liquid chromatography.
  
  
  RESULTS
  Hypertension was independently associated with incident stroke and stroke death after adjusting for important covariates including plasma log-transformed Hcy level. Relative to non-carriers of the MTHFR 677TT genotype with no hypertension, the adjusted odds ratio (95% confidence interval) of stroke and stroke death among hypertensive carriers of the MTHFR 677TT genotype was 10.6 (3.2 to 34.8), 5.8 (1.6 to 21.3), respectively. After excluding subjects with plasma Hcy above 20 μmol/L, the relative odds for stroke, but not for stroke death, was more significantly pronounced (OR = 24.1, 95% CI: 2.3 to 246.1) among subjects with moderate plasma Hcy levels. However, there was no significant interactive effect between hypertensive status and the MTHFR C677T variant on the odds of the two outcomes as estimated by interaction models.
  
  
  CONCLUSIONS
  Our major findings suggest that joint effects of the MTHFR C677T polymorphism and hypertension are consistent in predicting a significantly high risk of stroke. In addition for moderate plasma levels of Hcy, the predicted effects on the risk for the primary end point of stroke were more pronounced. These results may help to modify current approaches to vascular disease prevention in Chinese hypertensive patients.
authors.affiliation: a School of Life Sciences , Anhui University , Hefei , China.|b Institute of Biomedicine, Anhui Medical University , Hefei , China.
authors.forename: Shanqun
authors.initials: S
authors.lastname: Jiang
authors.affiliation: c Department of Cardiology , Peking University First Hospital , Beijing , China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Li
authors.affiliation: c Department of Cardiology , Peking University First Hospital , Beijing , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: d Faculty of Health Sciences , Simon Fraser University , Burnaby , Canada.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Venners
authors.affiliation: b Institute of Biomedicine, Anhui Medical University , Hefei , China.
authors.forename: Genfu
authors.initials: G
authors.lastname: Tang
authors.affiliation: b Institute of Biomedicine, Anhui Medical University , Hefei , China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: b Institute of Biomedicine, Anhui Medical University , Hefei , China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Li
authors.affiliation: b Institute of Biomedicine, Anhui Medical University , Hefei , China.|e National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital , Southern Medical University , Guangzhou , China.
authors.forename: Xiping
authors.initials: X
authors.lastname: Xu
authors.affiliation: e National Clinical Research Study Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital , Southern Medical University , Guangzhou , China.
authors.forename: Binyan
authors.initials: B
authors.lastname: Wang
authors.affiliation: c Department of Cardiology , Peking University First Hospital , Beijing , China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huo
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005215:Fasting / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000453:epidemiology*; D008137:Longitudinal Studies; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: MTHFR C677T polymorphism; nested case-control study; stroke