PMID- 20515676
OWN - NLM
STAT- MEDLINE
DCOM- 20101112
LR  - 20211020
IS  - 1873-3492 (Electronic)
IS  - 0009-8981 (Linking)
VI  - 411
IP  - 19-20
DP  - 2010 Oct 9
TI  - Gene variation of the transient receptor potential cation channel, subfamily M, 
      member 2 (TRPM2) and type 2 diabetes mellitus: A case-control study.
PG  - 1437-40
LID - 10.1016/j.cca.2010.05.036 [doi]
AB  - 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.
CI  - Copyright 2010 Elsevier B.V. All rights reserved.
FAU - Romero, Jose R
AU  - Romero JR
AD  - 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
FAU - Germer, Soren
AU  - Germer S
FAU - Castonguay, Amy J
AU  - Castonguay AJ
FAU - Barton, Nathaniel S
AU  - Barton NS
FAU - Martin, Mitchell
AU  - Martin M
FAU - Zee, Robert Y L
AU  - Zee RY
LA  - eng
GR  - R01 HL096518/HL/NHLBI NIH HHS/United States
GR  - R01 HL096518-01/HL/NHLBI NIH HHS/United States
GR  - R01-HL096518/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100601
PL  - Netherlands
TA  - Clin Chim Acta
JT  - Clinica chimica acta; international journal of clinical chemistry
JID - 1302422
RN  - 0 (TRPM Cation Channels)
RN  - 0 (TRPM2 protein, human)
SB  - IM
MH  - Adult
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 2/*genetics/physiopathology
MH  - Female
MH  - *Genetic Association Studies
MH  - Haplotypes
MH  - Homeostasis
MH  - Humans
MH  - Insulin Resistance
MH  - Insulin-Secreting Cells/physiology
MH  - Male
MH  - *Polymorphism, Single Nucleotide
MH  - Risk Factors
MH  - TRPM Cation Channels/*genetics
EDAT- 2010/06/03 06:00
MHDA- 2010/11/13 06:00
CRDT- 2010/06/03 06:00
PHST- 2010/04/30 00:00 [received]
PHST- 2010/05/21 00:00 [revised]
PHST- 2010/05/23 00:00 [accepted]
PHST- 2010/06/03 06:00 [entrez]
PHST- 2010/06/03 06:00 [pubmed]
PHST- 2010/11/13 06:00 [medline]
AID - S0009-8981(10)00369-4 [pii]
AID - 10.1016/j.cca.2010.05.036 [doi]
PST - ppublish
SO  - Clin Chim Acta. 2010 Oct 9;411(19-20):1437-40. doi: 10.1016/j.cca.2010.05.036. 
      Epub 2010 Jun 1.