ACE and Subarachnoid Hemorrhage: Strategies for Genetics of Stroke

Abstract

To the Editor: I thank Slowik et al for their article investigating the angiotensin-converting enzyme ( ACE ) insertion/deletion (I/D) polymorphism in subarachnoid hemorrhage (SAH).1 I wish to comment on several aspects of this article related to the design of genetic association studies for complex disorders such as SAH, which are important in interpreting their findings. It is impressive to note the high odds ratios achieved, however this study was less than half the size of the one it aimed to confirm.2 The populations of the 2 studies were of European origin and the allele frequencies were also similar. Using calculations previously described3 and the data from Keramatipour et al,2 an estimated sample size of 600 subjects is required to show the presence of an association of ACE I/D with SAH with 80% power. It is surprising that Slowik et al achieved twice as high an odds ratio with half the sample size. The small sample size of this study could have resulted in a type 1 error. ACE I/D polymorphism has been extensively studied in several disorders with conflicting results. Interestingly, Zhu et al showed that the I/D polymorphism is not functional and its association with elevated plasma ACE levels is secondary to a linkage disequilibrium (LD) effect.4 We recently showed this to be the case for the association of the I/D …