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Blood, Vol. 94 No. 11 (December 1), 1999:
pp. 3678-3682
Lipoprotein (a) and Genetic Polymorphisms of Clotting Factor V,
Prothrombin, and Methylenetetrahydrofolate Reductase Are Risk Factors
of Spontaneous Ischemic Stroke in Childhood
Ulrike Nowak-Göttl,
Ronald Sträter,
Achim Heinecke,
Ralf Junker,
Hans-Georg Koch,
Gerhard Schuierer, and
Arnold von
Eckardstein for the Childhood Stroke Study Group
From the Department of Paediatrics, Institute of Clinical Chemistry
and Laboratory Medicine and Institute of Arteriosclerosis Research,
Institute of Medical Statistics, and Institute of Clinical Radiology,
Westphalian Wilhelms-University Münster, Münster, Germany.
Ischemic stroke is a rare event in childhood. In approximately one
third of cases no obvious underlying cause or disorder can be detected.
We investigated the importance of genetic risk factors of venous
thromboembolism in childhood or stroke in adulthood as risk factors for
spontaneous ischemic stroke in children. One hundred forty-eight
Caucasian infants and children (aged 0.5 to 16 years) with stroke and
296 age-matched controls from the same geographic areas as the patients
were analyzed for increased lipoprotein (a) [Lp(a)] levels >30
mg/dL; for the presence of the factor V (FV) G1691A mutation, the
prothrombin (PT) G20210A variant, and the TT677 genotype of
methylenetetrahydrofolate reductase (MTHFR); and deficiencies of
protein C, protein S, and antithrombin. The following frequencies
(patients v controls), odds ratios (ORs), and confidence
intervals (CIs) of single risk factors were found: Lp(a) >30 mg/dL
(26.4% v 4.7%; OR/CI, 7.2/3.8 to 13.8; P < .0001), FV G1691A (20.2% v 4%; OR/CI, 6/2.97 to 12.1; P < .0001), protein C deficiency (6% v 0.67%; OR/CI, 9.5/2 to
44.6; P = .001), PT G20210A (6% v 1.3%; OR/CI,
4.7/1.4 to 15.6; P = .01), and the MTHFR TT677 genotype
(23.6% v 10.4%; OR/CI, 2.4/1.53 to 4.5; P < .0001).
A combination of the heterozygous FV G1691A mutation with increased
Lp(a) (n = 11) or the MTHFR TT677 genotype (n = 5) was found in
10.8% of cases, but only 0.3% of controls (OR/CI, 35.75/4.7 to 272;
P < .0001). Increased Lp (a) levels, the FV G1691A mutation,
protein C deficiency, the prothrombin G20210A variant, and the MTHFR
TT677 are important risk factors for spontaneous ischemic stroke in childhood.
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