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(Stroke. 2009;40:2965.)
© 2009 American Heart Association, Inc.

Original Contributions

Gene Variation of the Transient Receptor Potential Cation Channel, Subfamily M, Member 7 (TRPM7), and Risk of Incident Ischemic Stroke

Prospective, Nested, Case-Control Study

José R. Romero; Paul M. Ridker Robert Y.L. Zee

From the Division of Endocrinology, Diabetes, and Hypertension (J.R.R.) and the Division of Preventive Medicine (P.M.R., R.Y.L.Z.), Brigham and Women’s Hospital, and Harvard Medical School, Boston, Mass.

Correspondence to Dr José R. Romero, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, 221 Longwood Ave, Boston, MA 02115. E-mail jromero{at}rics.bwh.harvard.edu; or Dr Robert Y.L. Zee, Division of Preventive Medicine, Brigham and Women’s Hospital, 900 Commonwealth Ave East, Boston, MA 02215. E-mail rzee@rics.bwh.harvard.edu

Background and Purpose— Transient receptor potential cation channel, subfamily M, member 7 (TRPM7), has been implicated in ischemic brain damage, a major source of morbidity and mortality in westernized society. We hypothesized that TRPM7 gene variation might play a role in the risk of ischemic stroke.

Methods— From a group of DNA samples collected at baseline in a prospective cohort of 14 916 initially healthy American men, we assessed 16 TRPM7 tag–single-nucleotide polymorphisms (SNPs) (dbSNP: rs11854949, rs4775899, rs11635825, rs12905120, rs16973487, rs7173321, rs7163283, rs17520378, rs17520350, rs4775892, rs7174839, rs17645523, rs3109894, rs616256, rs11070795, and rs313158) from 245 white men who subsequently had an incident ischemic stroke and from 245 age- and smoking habit–matched white men who remained free of reported vascular disease during follow-up (controls).

Results— All SNPs examined were in Hardy-Weinberg equilibrium. Overall allele, genotype, and haplotype distributions were similar between cases and controls. Marker-by-marker conditional logistic-regression analysis, adjusted for potential risk factors, showed no evidence for an association between any of the SNPs tested and ischemic stroke. Further investigation with an Entropy Blocker–defined, haplotype-based approach showed similar null findings. Prespecified analysis limited to participants without baseline diabetes and hypertension (ie, low-risk group) again showed similar null findings.

Conclusions— The present prospective investigation provides no evidence of a role for the TRPM7 gene in the risk of incident ischemic stroke.

Key Words: TRPM7 • tag–single-nucleotide polymorphisms • ischemic stroke • risk factors