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.
OBJECTIVE
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.
Romero
José R
JR
Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, MA 02115, USA. jromero@rics.bwh.harvard.edu
Ridker
Paul M
PM
Zee
Robert Y L
RY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases; D012307:Risk Factors; D020521:Stroke / Q000235:genetics*; D050053:TRPM Cation Channels / Q000235:genetics*
D050053:TRPM Cation Channels; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human