Published Online
on March 13, 2003

A more recent version of this article appeared on April 1, 2003

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Submitted on September 24, 2002
Accepted on October 11, 2002

Fibrinogen Gene Promoter -455 A Allele as a Risk Factor for Lacunar Stroke

M. Martiskainen MD; T. Pohjasvaara MD, PhD; J. Mikkelsson MD, PhD; R. Mäntylä MD; T. Kunnas MSc; P. Laippala PhD; E. Ilveskoski MD, PhD; M. Kaste MD, PhD; P. J. Karhunen MD, PhD^*; and T. Erkinjuntti MD, PhD

From the School of Medicine (M.M., J.M., T.K., E.I., P.J.K.) and School of Public Health (P.L.), University of Tampere, Tampere, Finland; Centre of Laboratory (M.M., J.M., T.K., E.I., P.J.K.) and Research Unit (P.L.), Tampere University Hospital, Tampere, Finland; Memory Research and Stroke Units, Department of Clinical Neurosciences (T.P., M.K., T.E.), and Department of Radiology (R.M., P.L.), Helsinki University Central Hospital, Helsinki, Finland; and Lohja District Hospital (T.P.), Lohja, Finland.

^* To whom correspondence should be addressed. E-mail: pekka.karhunen{at}uta.fi.

Background and Purpose--Elevated fibrinogen levels are suggested to increase the risk of myocardial infarction and stroke. Carriers of the A allele of the fibrinogen -455G/A polymorphism have increased plasma fibrinogen levels. We studied the association of this polymorphism with stroke subtype in the Stroke Aging Memory (SAM) cohort.

Methods--The SAM cohort comprises 486 consecutive patients 55 to 85 years of age who, 3 months after ischemic stroke, completed a detailed stroke assessment. Stroke subtypes were examined with MRI. -455G/A genotype was determined by polymerase chain reaction. MRI and genotype data were available for the 299 patients who constitute the present study population.

Results--Genotype distributions were 64.9% (GG), 31.8% (GA), and 3.3% (AA). In a logistic regression model with age, sex, hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, myocardial infarction, arrhythmia, atrial fibrillation, peripheral arterial disease, and smoking as possible confounders, there was a significant association between A+ genotype and 3 lacunar infarcts (odds ratio [OR], 2.57; 95% CI, 1.23 to 5.36; P=0.01). Hypertensive patients carrying the A allele had increased risk (OR, 4.24; 95% CI, 1.29 to 13.99; P=0.02) for 3 lacunar infarcts. A similar increase in risk was observed among smokers with the A+ genotype (OR, 2.67; 95% CI, 0.92 to 7.77; P=0.07).

Conclusions--Stroke patients carrying the A allele of the B-fibrinogen -455G/A polymorphism frequently presented with multiple lacunar infarcts. This association was stronger among hypertensives and smokers. These associations suggest that the A allele may predispose to atherothrombotic events in cerebrovascular circulation.

Key words: fibrinogen • genetics • infarcts • lacunar infarction • stroke

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