BACKGROUND: Disordered cellular calcium regulation has been implicated in the 
pathophysiology of diabetes through mechanisms that remain unresolved. The 
non-selective calcium channel, transient receptor potential cation channel, 
subfamily M, member 2 (TRPM2), has been recently reported to play a role in 
insulin secretion by pancreatic beta-cells. We hypothesized that gene variation 
of TRPM2 may play a role in the pathophysiology of type 2 diabetes mellitus 
(T2DM).
METHODS: Using a case-control study from a community-based population sample of 
the Boston metropolitan area (all whites: 455 controls and 467 cases), we 
assessed the relationship of 9 TRPM2 tag-SNPs with (i) diabetes-related 
intermediate phenotypes and (ii) the presence of T2DM.
RESULT: All SNPs examined were in Hardy-Weinberg equilibrium. Overall allele, 
genotype, and haplotype distributions were similar between cases and controls. 
Three TRPM2 variants (rs2838553, rs2838554 and rs4818917) were associated with 
homeostasis model assessment of beta-cell function (HOMA-%B), but not with 
HOMA-insulin resistance (HOMA-IR), fasting glucose levels nor hemoglobin A1c 
levels. Marker-by-marker logistic regression analysis, adjusted for potential 
risk factors, showed no evidence for an association of any of the tag-SNPs 
tested with T2DM. Further investigation using an entropy blocker-defined 
haplotype-based approach showed similar null findings.
CONCLUSIONS: The present investigation found no evidence for an association of 
the variants tested with T2DM, although HOMA-%B was negatively associated with 
three TRPM2 variants (rs2838553, rs2838554 and rs4818917). More importantly, our 
present findings require replication/confirmation in future large-scale, 
prospective investigations.