title: A common haplotype for the 677T thermolabile variant of the 5,10-methylenetetrahydrofolate reductase gene in thrombophilic patients and controls.
abstract: The common polymorphic transition 677C>T in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene causes a thermolabile enzyme variant. This variant is associated with moderate hyperhomocysteinemia, a risk factor for vascular disease and thrombophilia. Up to now, it remained unclear if the thermolabile MTHFR variant either directly predisposes to vascular disease, or if 677T is only a genetic marker for another causative genetic alteration in cis. Aim of this study was to characterize the genetic background of 677T-alleles by haplotype analysis. We analyzed 25 individuals of German descent homozygous for 677T: nine young patients, who had suffered from thromboembolic events, and 16 healthy controls. The results of this study demonstrate that the 677T alleles are associated with a common haplotype most likely due to a founder effect and that the 677T haplotype was the same in the healthy and the thrombophilic German subjects.
authors.affiliation: Universitaetsklinikum Muenster, Klinik und Poliklinik fuer Kinderheilkunde, Muenster, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Linnebank
authors.forename: A
authors.initials: A
authors.lastname: Homberger
authors.forename: U
authors.initials: U
authors.lastname: Nowak-Göttl
authors.forename: H G
authors.initials: HG
authors.lastname: Koch
mesh_terms: D000483:Alleles; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004795:Enzyme Stability; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation; D013696:Temperature; D019851:Thrombophilia / Q000201:enzymology / Q000235:genetics*
chemical_list: D004247:DNA; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)