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Population specific impact of genetic variants in KCNJ11 gene to type 2 diabetes: a case-control and meta-analysis study.

Abstract Potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene have a key role in insulin secretion and is of substantial interest as a candidate gene for type 2 diabetes (T2D). The current work was performed to delineate the genetic influence of KCNJ11 polymorphisms on risk of T2D in South Indian population through case-control association study along with systematic review and meta-analysis.
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Mayor MeshTerms
Keywords
Journal Title plos one
Publication Year Start




PMID- 25247988
OWN - NLM
STAT- MEDLINE
DA  - 20140924
DCOM- 20150622
LR  - 20151029
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 9
DP  - 2014
TI  - Population specific impact of genetic variants in KCNJ11 gene to type 2 diabetes:
      a case-control and meta-analysis study.
PG  - e107021
LID - 10.1371/journal.pone.0107021 [doi]
AB  - BACKGROUND AND OBJECTIVES: Potassium inwardly rectifying channel, subfamily J,
      member 11 (KCNJ11) gene have a key role in insulin secretion and is of
      substantial interest as a candidate gene for type 2 diabetes (T2D). The current
      work was performed to delineate the genetic influence of KCNJ11 polymorphisms on 
      risk of T2D in South Indian population through case-control association study
      along with systematic review and meta-analysis. METHODS: A case-control study of 
      400 T2D cases and controls of South Indian origin were performed to analyze the
      association of KCNJ11 polymorphisms (rs5219, rs5215, rs41282930, rs1800467) and
      copy number variations (CNV) on the risk of T2D. In addition a systematic review 
      and meta-analysis for KCNJ11 rs5219 was conducted in 3,831 cases and 3,543
      controls from 5 published reports from South-Asian population by searching
      various databases. Odds ratio with 95% confidence interval (CI) was used to
      assess the association strength. Cochran's Q, I2 statistics were used to study
      heterogeneity between the eligible studies. RESULTS: KCNJ11 rs5215, C-G-C-C
      haplotype and two loci analysis (rs5219 vs rs1800467) showed a significant
      association with T2D but CNV analysis did not show significant variation between 
      T2D cases and control subjects. Lower age of disease onset (P = 0.04) and higher 
      body mass index (BMI) (P = 0.04) were associated with rs5219 TT genotype in T2D
      patients. The meta-analysis of KCNJ11 rs5219 on South Asian population showed no 
      association on susceptibility to T2D with an overall pooled OR = 0.98, 95% CI =
      0.83-1.16. Stratification analysis showed East Asian population and global
      population were associated with T2D when compared to South Asians. CONCLUSION:
      KCNJ11 rs5219 is not independently associated with T2D in South-Indian population
      and our meta-analysis suggests that KCNJ11 polymorphism (rs5219) is associated
      with risk of T2D in East Asian population and global population but this outcome 
      could not be replicated in South Asian sub groups.
FAU - Phani, Nagaraja M
AU  - Phani NM
AD  - Division of Biotechnology, School of Life Sciences, Manipal University, Manipal, 
      Karnataka, India.
FAU - Guddattu, Vasudeva
AU  - Guddattu V
AD  - Department of Statistics, Manipal University, Manipal, Karnataka, India.
FAU - Bellampalli, Ravishankara
AU  - Bellampalli R
AD  - Division of Biotechnology, School of Life Sciences, Manipal University, Manipal, 
      Karnataka, India.
FAU - Seenappa, Venu
AU  - Seenappa V
AD  - Division of Biotechnology, School of Life Sciences, Manipal University, Manipal, 
      Karnataka, India.
FAU - Adhikari, Prabha
AU  - Adhikari P
AD  - Department of Medicine, Kasturba Medical College, Manipal University, Mangalore, 
      Karnataka, India.
FAU - Nagri, Shivashankara K
AU  - Nagri SK
AD  - Department of Medicine, Kasturba Medical College, Manipal University, Manipal,
      Karnataka, India.
FAU - D Souza, Sydney C
AU  - D Souza SC
AD  - Department of Medicine, Kasturba Medical College, Manipal University, Mangalore, 
      Karnataka, India.
FAU - Mundyat, Gopinath P
AU  - Mundyat GP
AD  - Division of Biotechnology, School of Life Sciences, Manipal University, Manipal, 
      Karnataka, India.
FAU - Satyamoorthy, Kapaettu
AU  - Satyamoorthy K
AD  - Division of Biotechnology, School of Life Sciences, Manipal University, Manipal, 
      Karnataka, India.
FAU - Rai, Padmalatha S
AU  - Rai PS
AD  - Division of Biotechnology, School of Life Sciences, Manipal University, Manipal, 
      Karnataka, India.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20140923
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Kir6.2 channel)
RN  - 0 (Potassium Channels, Inwardly Rectifying)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Asian Continental Ancestry Group/*genetics
MH  - Case-Control Studies
MH  - DNA Copy Number Variations
MH  - Diabetes Mellitus, Type 2/*ethnology/*genetics
MH  - European Continental Ancestry Group/*genetics
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - Genetic Variation
MH  - Humans
MH  - India
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
MH  - Potassium Channels, Inwardly Rectifying/*genetics
PMC - PMC4172481
OID - NLM: PMC4172481
EDAT- 2014/09/24 06:00
MHDA- 2015/06/24 06:00
CRDT- 2014/09/24 06:00
PHST- 2014/04/24 [received]
PHST- 2014/08/04 [accepted]
AID - 10.1371/journal.pone.0107021 [doi]
AID - PONE-D-14-17996 [pii]
PST - epublish
SO  - PLoS One. 2014 Sep 23;9(9):e107021. doi: 10.1371/journal.pone.0107021.
      eCollection 2014.

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