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(Circulation. 2000;101:2393.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

A Common Mutation in Lipoprotein Lipase Confers a 2-Fold Increase in Risk of Ischemic Cerebrovascular Disease in Women but Not in Men

Hans H. Wittrup, MD, PhD; Børge G. Nordestgaard, MD, DMSc; Henrik Sillesen, MD, DMSc; Peter Schnohr, MD; Anne Tybjærg-Hansen, MD, DMSc

From the Department of Clinical Biochemistry, Herlev and Glostrup University Hospitals (H.H.W., B.G.N., A.T.-H.), the Copenhagen City Heart Study, Bispebjerg University Hospital (B.G.N., P.S., A.T.-H.), and the Department of Vascular Surgery, Gentofte University Hospital (H.S.), Copenhagen, Denmark.

Correspondence to Anne Tybjærg-Hansen, Department of Clinical Biochemistry, Rigshospitalet 4111, National University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. E-mail ath{at}image.dk

Background—We previously showed that the common Asn291Ser substitution in lipoprotein lipase is associated with elevated plasma triglyceride levels and a 2-fold increase in the risk of ischemic heart disease in women but not men. In this study, we tested the hypothesis that this substitution is also associated with an increased risk of ischemic cerebrovascular disease (ICVD).

Methods and Results—We compared 260 patients who had nonfatal ICVD and carotid stenosis 50% with 1560 age-matched controls and also compared 205 Copenhagen City Heart Study cases who had nonfatal ICVD with 1210 age-matched controls. All subjects were white and from Denmark. Overall, no significant difference was observed between carrier frequencies among those with and without ICVD; however, sex interacted with genotype in predicting ICVD in the ICVD and carotid stenosis cases (P=0.02). In Copenhagen City Heart Study cases, sex was not significant (P=0.18). Odds ratios for ICVD in female mutation carriers were 2.9 (95% confidence interval [CI], 1.3 to 6.4) and 1.9 (95% CI, 0.8 to 4.6) in ICVD plus carotid stenosis cases and Copenhagen City Heart Study cases, respectively. Equivalent values in male mutation carriers were 0.8 (95% CI, 0.3 to 1.8) and 0.8 (95% CI, 0.3 to 2.0), respectively. These results were similar in analyses that also allowed for other conventional cardiovascular risk factors.

Conclusions—These results suggest that the Asn291Ser substitution in lipoprotein lipase is not associated with nonfatal ICVD in men but that it possibly confers a 2-fold risk in women.

Key Words: genetics • polymorphism (genetic) • triglycerides • cholesterol • cerebral ischemia

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