Gene variation of the transient receptor potential cation channel, subfamily M, member 2 (TRPM2) and type 2 diabetes mellitus: A case-control study.
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.


RESULTS
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.
Divisions of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA, USA. jromero@rics.bwh.harvard.edu
José R
JR
Romero
Soren
S
Germer
Amy J
AJ
Castonguay
Nathaniel S
NS
Barton
Mitchell
M
Martin
Robert Y L
RY
Zee
D000328:Adult; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000502:physiology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D050053:TRPM Cation Channels / Q000235:genetics*
D050053:TRPM Cation Channels; C121934:TRPM2 protein, human