PMID- 23967108
OWN - NLM
STAT- MEDLINE
DCOM- 20140318
LR  - 20231106
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 8
DP  - 2013
TI  - Genetic susceptible locus in NOTCH2 interacts with arsenic in drinking water on 
      risk of type 2 diabetes.
PG  - e70792
LID - 10.1371/journal.pone.0070792 [doi]
LID - e70792
AB  - BACKGROUND: Chronic exposure to arsenic in drinking water is associated with 
      increased risk of type 2 diabetes mellitus (T2DM) but the underlying molecular 
      mechanism remains unclear. OBJECTIVES: This study evaluated the interaction 
      between single nucleotide polymorphisms (SNPs) in genes associated with diabetes 
      and arsenic exposure in drinking water on the risk of developing T2DM. METHODS: 
      In 2009-2011, we conducted a follow up study of 957 Bangladeshi adults who 
      participated in a case-control study of arsenic-induced skin lesions in 
      2001-2003. Logistic regression models were used to evaluate the association 
      between 38 SNPs in 18 genes and risk of T2DM measured at follow up. T2DM was 
      defined as having a blood hemoglobin A1C level greater than or equal to 6.5% at 
      follow-up. Arsenic exposure was characterized by drinking water samples collected 
      from participants' tubewells. False discovery rates were applied in the analysis 
      to control for multiple comparisons. RESULTS: Median arsenic levels in 2001-2003 
      were higher among diabetic participants compared with non-diabetic ones (71.6 
      microg/L vs. 12.5 microg/L, p-value <0.001). Three SNPs in ADAMTS9 were nominally 
      associated with increased risk of T2DM (rs17070905, Odds Ratio (OR)  = 2.30, 95% 
      confidence interval (CI) 1.17-4.50; rs17070967, OR = 2.02, 95%CI 1.00-4.06; 
      rs6766801, OR = 2.33, 95%CI 1.18-4.60), but these associations did not reach the 
      statistical significance after adjusting for multiple comparisons. A significant 
      interaction between arsenic and NOTCH2 (rs699780) was observed which 
      significantly increased the risk of T2DM (p for interaction = 0.003; 
      q-value = 0.021). Further restricted analysis among participants exposed to water 
      arsenic of less than 148 microg/L showed consistent results for interaction between 
      the NOTCH2 variant and arsenic exposure on T2DM (p for interaction  = 0.048; 
      q-value = 0.004). CONCLUSIONS: These findings suggest that genetic variation in 
      NOTCH2 increased susceptibility to T2DM among people exposed to inorganic 
      arsenic. Additionally, genetic variants in ADAMTS9 may increase the risk of T2DM.
FAU - Pan, Wen-Chi
AU  - Pan WC
AD  - Department of Environmental Health, Harvard School of Public Health, Boston, 
      Massachusetts, United States of America.
FAU - Kile, Molly L
AU  - Kile ML
FAU - Seow, Wei Jie
AU  - Seow WJ
FAU - Lin, Xihong
AU  - Lin X
FAU - Quamruzzaman, Quazi
AU  - Quamruzzaman Q
FAU - Rahman, Mahmuder
AU  - Rahman M
FAU - Mahiuddin, Golam
AU  - Mahiuddin G
FAU - Mostofa, Golam
AU  - Mostofa G
FAU - Lu, Quan
AU  - Lu Q
FAU - Christiani, David C
AU  - Christiani DC
LA  - eng
GR  - R01ES011622/ES/NIEHS NIH HHS/United States
GR  - P30 ES000002/ES/NIEHS NIH HHS/United States
GR  - P42ES016454/ES/NIEHS NIH HHS/United States
GR  - K01 ES017800/ES/NIEHS NIH HHS/United States
GR  - R01 ES022230/ES/NIEHS NIH HHS/United States
GR  - P30ES000002/ES/NIEHS NIH HHS/United States
GR  - P42 ES016454/ES/NIEHS NIH HHS/United States
GR  - R01ES022230/ES/NIEHS NIH HHS/United States
GR  - R01 ES011622/ES/NIEHS NIH HHS/United States
GR  - K01ES017800/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130814
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Drinking Water)
RN  - 0 (Receptor, Notch2)
RN  - 0 (Water Pollutants, Chemical)
RN  - N712M78A8G (Arsenic)
SB  - IM
MH  - Adult
MH  - Arsenic/*toxicity
MH  - Diabetes Mellitus, Type 2/etiology/*genetics
MH  - Drinking Water/*chemistry
MH  - Environmental Exposure/adverse effects
MH  - Female
MH  - *Gene-Environment Interaction
MH  - Genetic Loci/*genetics
MH  - Genetic Predisposition to Disease/*genetics
MH  - Humans
MH  - Male
MH  - Polymorphism, Single Nucleotide
MH  - Receptor, Notch2/*genetics
MH  - Water Pollutants, Chemical/toxicity
PMC - PMC3743824
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/08/24 06:00
MHDA- 2014/03/19 06:00
PMCR- 2013/08/14
CRDT- 2013/08/23 06:00
PHST- 2013/03/13 00:00 [received]
PHST- 2013/06/24 00:00 [accepted]
PHST- 2013/08/23 06:00 [entrez]
PHST- 2013/08/24 06:00 [pubmed]
PHST- 2014/03/19 06:00 [medline]
PHST- 2013/08/14 00:00 [pmc-release]
AID - PONE-D-13-10685 [pii]
AID - 10.1371/journal.pone.0070792 [doi]
PST - epublish
SO  - PLoS One. 2013 Aug 14;8(8):e70792. doi: 10.1371/journal.pone.0070792. eCollection 
      2013.