Methylenetetrahydrofolate reductase polymorphism (C677T), hyperhomocysteinemia, and risk of ischemic cardiovascular disease and venous thromboembolism: prospective and case-control studies from the Copenhagen City Heart Study

Jeppe Frederiksen; Klaus Juul; Peer Grande; Gorm B Jensen; Torben V Schroeder; Anne Tybjaerg-Hansen; Børge G Nordestgaard

doi:http://dx.doi.org/10.1182/blood-2004-03-0897

Methylenetetrahydrofolate reductase polymorphism (C677T), hyperhomocysteinemia, and risk of ischemic cardiovascular disease and venous thromboembolism: prospective and case-control studies from the Copenhagen City Heart Study

Jeppe Frederiksen, Klaus Juul, Peer Grande, Gorm B Jensen, Torben V Schroeder, Anne Tybjaerg-Hansen, Børge G Nordestgaard

104 Citationer (Scopus)

Abstract

Hyperhomocysteinemia is associated with ischemic cardiovascular disease (ICD) and venous thromboembolism (VTE). We tested the hypothesis that methylenetetrahydrofolate reductase (MTHFR) C677T homozygosity with hyperhomocysteinemia is associated with ICD and VTE. First, 9238 randomly selected whites from the general population were followed for 23 years. Second, 2125 whites with ischemic heart disease and 836 whites with ischemic cerebrovascular disease were compared with 7568 controls from the general population. Plasma homocysteine was elevated 25% in homozygotes versus noncarriers (P <.001) and 19% in ICD/VTE cases versus controls (P <.001). In prospective studies adjusted hazard ratios for ICD and VTE for homozygotes versus noncarriers did not differ from 1.0. Furthermore, MTHFR C677T homozygosity was not associated with increased risk of ICD or VTE in subgroups after stratification for sex, age, cholesterol, high-density lipoprotein cholesterol, lipoprotein(a), fibrinogen, triglycerides, body mass index, smoking, diabetes mellitus, hypertension, and factor V Leiden genotype. Finally, in case-control studies odds ratios for ischemic heart disease and ischemic cerebrovascular disease in homozygotes versus noncarriers did not differ from 1.0. In conclusion, MTHFR C677T homozygosity with hyperhomocysteinemia is not associated with ICD or VTE; however, ICD/VTE is associated with hyperhomocysteinemia. Therefore, ICD and VTE may cause hyperhomocysteinemia, rather than vice versa.

Originalsprog	Engelsk
Tidsskrift	Blood
Vol/bind	104
Udgave nummer	10
Sider (fra-til)	3046-51
Antal sider	6
ISSN	0006-4971
DOI	https://doi.org/10.1182/blood-2004-03-0897
Status	Udgivet - 15 nov. 2004

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Citationsformater

Frederiksen, J., Juul, K., Grande, P., Jensen, G. B., Schroeder, T. V., Tybjaerg-Hansen, A., & Nordestgaard, B. G. (2004). Methylenetetrahydrofolate reductase polymorphism (C677T), hyperhomocysteinemia, and risk of ischemic cardiovascular disease and venous thromboembolism: prospective and case-control studies from the Copenhagen City Heart Study. Blood, 104(10), 3046-51. https://doi.org/10.1182/blood-2004-03-0897

Methylenetetrahydrofolate reductase polymorphism (C677T), hyperhomocysteinemia, and risk of ischemic cardiovascular disease and venous thromboembolism: prospective and case-control studies from the Copenhagen City Heart Study. / Frederiksen, Jeppe; Juul, Klaus; Grande, Peer et al.

I: Blood, Bind 104, Nr. 10, 15.11.2004, s. 3046-51.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Frederiksen, J, Juul, K, Grande, P, Jensen, GB, Schroeder, TV, Tybjaerg-Hansen, A & Nordestgaard, BG 2004, 'Methylenetetrahydrofolate reductase polymorphism (C677T), hyperhomocysteinemia, and risk of ischemic cardiovascular disease and venous thromboembolism: prospective and case-control studies from the Copenhagen City Heart Study', Blood, bind 104, nr. 10, s. 3046-51. https://doi.org/10.1182/blood-2004-03-0897

Frederiksen J, Juul K, Grande P, Jensen GB, Schroeder TV, Tybjaerg-Hansen A et al. Methylenetetrahydrofolate reductase polymorphism (C677T), hyperhomocysteinemia, and risk of ischemic cardiovascular disease and venous thromboembolism: prospective and case-control studies from the Copenhagen City Heart Study. Blood. 2004 nov. 15;104(10):3046-51. doi: http://dx.doi.org/10.1182/blood-2004-03-0897

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title = "Methylenetetrahydrofolate reductase polymorphism (C677T), hyperhomocysteinemia, and risk of ischemic cardiovascular disease and venous thromboembolism: prospective and case-control studies from the Copenhagen City Heart Study",

abstract = "Hyperhomocysteinemia is associated with ischemic cardiovascular disease (ICD) and venous thromboembolism (VTE). We tested the hypothesis that methylenetetrahydrofolate reductase (MTHFR) C677T homozygosity with hyperhomocysteinemia is associated with ICD and VTE. First, 9238 randomly selected whites from the general population were followed for 23 years. Second, 2125 whites with ischemic heart disease and 836 whites with ischemic cerebrovascular disease were compared with 7568 controls from the general population. Plasma homocysteine was elevated 25% in homozygotes versus noncarriers (P <.001) and 19% in ICD/VTE cases versus controls (P <.001). In prospective studies adjusted hazard ratios for ICD and VTE for homozygotes versus noncarriers did not differ from 1.0. Furthermore, MTHFR C677T homozygosity was not associated with increased risk of ICD or VTE in subgroups after stratification for sex, age, cholesterol, high-density lipoprotein cholesterol, lipoprotein(a), fibrinogen, triglycerides, body mass index, smoking, diabetes mellitus, hypertension, and factor V Leiden genotype. Finally, in case-control studies odds ratios for ischemic heart disease and ischemic cerebrovascular disease in homozygotes versus noncarriers did not differ from 1.0. In conclusion, MTHFR C677T homozygosity with hyperhomocysteinemia is not associated with ICD or VTE; however, ICD/VTE is associated with hyperhomocysteinemia. Therefore, ICD and VTE may cause hyperhomocysteinemia, rather than vice versa.",

author = "Jeppe Frederiksen and Klaus Juul and Peer Grande and Jensen, {Gorm B} and Schroeder, {Torben V} and Anne Tybjaerg-Hansen and Nordestgaard, {B{\o}rge G}",

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T1 - Methylenetetrahydrofolate reductase polymorphism (C677T), hyperhomocysteinemia, and risk of ischemic cardiovascular disease and venous thromboembolism: prospective and case-control studies from the Copenhagen City Heart Study

AU - Frederiksen, Jeppe

AU - Juul, Klaus

AU - Grande, Peer

AU - Jensen, Gorm B

AU - Schroeder, Torben V

AU - Tybjaerg-Hansen, Anne

AU - Nordestgaard, Børge G

PY - 2004/11/15

Y1 - 2004/11/15

N2 - Hyperhomocysteinemia is associated with ischemic cardiovascular disease (ICD) and venous thromboembolism (VTE). We tested the hypothesis that methylenetetrahydrofolate reductase (MTHFR) C677T homozygosity with hyperhomocysteinemia is associated with ICD and VTE. First, 9238 randomly selected whites from the general population were followed for 23 years. Second, 2125 whites with ischemic heart disease and 836 whites with ischemic cerebrovascular disease were compared with 7568 controls from the general population. Plasma homocysteine was elevated 25% in homozygotes versus noncarriers (P <.001) and 19% in ICD/VTE cases versus controls (P <.001). In prospective studies adjusted hazard ratios for ICD and VTE for homozygotes versus noncarriers did not differ from 1.0. Furthermore, MTHFR C677T homozygosity was not associated with increased risk of ICD or VTE in subgroups after stratification for sex, age, cholesterol, high-density lipoprotein cholesterol, lipoprotein(a), fibrinogen, triglycerides, body mass index, smoking, diabetes mellitus, hypertension, and factor V Leiden genotype. Finally, in case-control studies odds ratios for ischemic heart disease and ischemic cerebrovascular disease in homozygotes versus noncarriers did not differ from 1.0. In conclusion, MTHFR C677T homozygosity with hyperhomocysteinemia is not associated with ICD or VTE; however, ICD/VTE is associated with hyperhomocysteinemia. Therefore, ICD and VTE may cause hyperhomocysteinemia, rather than vice versa.

AB - Hyperhomocysteinemia is associated with ischemic cardiovascular disease (ICD) and venous thromboembolism (VTE). We tested the hypothesis that methylenetetrahydrofolate reductase (MTHFR) C677T homozygosity with hyperhomocysteinemia is associated with ICD and VTE. First, 9238 randomly selected whites from the general population were followed for 23 years. Second, 2125 whites with ischemic heart disease and 836 whites with ischemic cerebrovascular disease were compared with 7568 controls from the general population. Plasma homocysteine was elevated 25% in homozygotes versus noncarriers (P <.001) and 19% in ICD/VTE cases versus controls (P <.001). In prospective studies adjusted hazard ratios for ICD and VTE for homozygotes versus noncarriers did not differ from 1.0. Furthermore, MTHFR C677T homozygosity was not associated with increased risk of ICD or VTE in subgroups after stratification for sex, age, cholesterol, high-density lipoprotein cholesterol, lipoprotein(a), fibrinogen, triglycerides, body mass index, smoking, diabetes mellitus, hypertension, and factor V Leiden genotype. Finally, in case-control studies odds ratios for ischemic heart disease and ischemic cerebrovascular disease in homozygotes versus noncarriers did not differ from 1.0. In conclusion, MTHFR C677T homozygosity with hyperhomocysteinemia is not associated with ICD or VTE; however, ICD/VTE is associated with hyperhomocysteinemia. Therefore, ICD and VTE may cause hyperhomocysteinemia, rather than vice versa.

U2 - http://dx.doi.org/10.1182/blood-2004-03-0897

DO - http://dx.doi.org/10.1182/blood-2004-03-0897

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