title: The 677T genotype of the common MTHFR thermolabile variant and fasting homocysteine in childhood venous thrombosis.
abstract: Controlled data on the association of MTHFR genotypes, hyperhomocysteinaemia and their interaction with factor V G1691A with childhood thrombosis are not yet available. Therefore we conducted a case-control study comparing 141 childhood patients with venous thrombosis with 345 healthy controls. The MTHFR C677T genotypes, FV G1691A and prothrombin G20210A were evaluated; in addition, fasting homocysteine concentrations were measured in a subgroup of 60 children and 80 healthy controls. 10.4% of the healthy control population showed the MTHFR TT genotype, 34.2% the CT genotype and 55.4% the CC variant. MTHFR genotypes account for fasting homocysteine concentrations in healthy controls (CC: 5.5 micromol/l (4-7.2); CT: 7 micromol/l (3.9-9.8); TT: 12.1 micromol/l (7.7-13.3)) with an upper age-specific 95th percentile of 8.3 micromol/l. The following frequencies (patients versus controls), odds ratios (OR) and 95% confidence intervals (CI) were found for single defects: MTHFR 677TT genotype (10.6% vs. 10.4%; OR/CI: 1.02/0.54-1.93; P = 0.99) and CT genotype (43.8% vs. 34.2%; OR/CI: 2.12/1.42-3.16; P = 0.0000). A combination of FV G1691A mutation and MTHFR 677CT genotype was found in 9.9% of patients and in 2.9% of the controls (OR/CI: 3.8/1.64-8.75; P = 0.027). Fasting homocysteine median (range) concentrations in the patient group were significantly higher than in the controls (7 micromol/l (3-23) vs. 5.5 micromol/l (3-8.4): P = 0.0004), and homocysteine concentrations >8.3 micromol/l were found in 40% of patients vs. 2.5% of the controls (OR/CI: 22/2.64-183; P = 0.0003). Conclusion Data of this childhood case-control study suggest that mildly elevated fasting homocysteine concentrations >8.3 micromol/l and the CT genotype of the MTHFR C677T variant are significant risk factors for venous vascular occlusion in children.
authors.affiliation: Department of Paediatrics, University Hospital, Münster, Germany. kochha@uni-muenster.de
authors.forename: H G
authors.initials: HG
authors.lastname: Koch
authors.forename: P
authors.initials: P
authors.lastname: Nabel
authors.forename: R
authors.initials: R
authors.lastname: Junker
authors.forename: K
authors.initials: K
authors.lastname: Auberger
authors.forename: R
authors.initials: R
authors.lastname: Schobess
authors.forename: A
authors.initials: A
authors.lastname: Homberger
authors.forename: M
authors.initials: M
authors.lastname: Linnebank
authors.forename: U
authors.initials: U
authors.lastname: Nowak-Göttl
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005165:Factor V / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000235:genetics; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D020412:Multifactorial Inheritance; D016017:Odds Ratio; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D015995:Prevalence; D011516:Prothrombin / Q000235:genetics; D012307:Risk Factors; D018709:Statistics, Nonparametric; D020246:Venous Thrombosis / Q000097:blood* / Q000235:genetics*
chemical_list: D006710:Homocysteine; D005165:Factor V; D011516:Prothrombin; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)