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Investigation of Type 2 Diabetes Risk Alleles Support CDKN2A/B, CDKAL1, and TCF7L2 As Susceptibility Genes in a Han Chinese Cohort

Wen, Jie ; Rönn, Tina LU ; Olsson, Anders H LU ; Yang, Zhen ; Lu, Bin ; Du, Yieping ; Groop, Leif LU ; Ling, Charlotte LU orcid and Hu, Renming (2010) In PLoS ONE 5(2).
Abstract
Background: Recent genome-wide association studies (GWASs) have reported several genetic variants to be reproducibly associated with type 2 diabetes. Additional variants have also been detected from a metaanalysis of three GWASs, performed in populations of European ancestry. In the present study, we evaluated the influence of 17 genetic variants from 15 candidate loci, identified in type 2 diabetes GWASs and the metaanalysis, in a Han Chinese cohort. Methodology/Principal Findings: Selected type 2 diabetes-associated genetic variants were genotyped in 1,165 type 2 diabetic patients and 1,136 normoglycemic control individuals of Southern Han Chinese ancestry. The OR for risk of developing type 2 diabetes was calculated using a logistic... (More)
Background: Recent genome-wide association studies (GWASs) have reported several genetic variants to be reproducibly associated with type 2 diabetes. Additional variants have also been detected from a metaanalysis of three GWASs, performed in populations of European ancestry. In the present study, we evaluated the influence of 17 genetic variants from 15 candidate loci, identified in type 2 diabetes GWASs and the metaanalysis, in a Han Chinese cohort. Methodology/Principal Findings: Selected type 2 diabetes-associated genetic variants were genotyped in 1,165 type 2 diabetic patients and 1,136 normoglycemic control individuals of Southern Han Chinese ancestry. The OR for risk of developing type 2 diabetes was calculated using a logistic regression model adjusted for age, sex, and BMI. Genotype-phenotype associations were tested using a multivariate linear regression model. Genetic variants in CDKN2A/B, CDKAL1, TCF7L2, TCF2, MC4R, and PPARG showed a nominal association with type 2 diabetes (P <= 0.05), of whom the three first would stand correction for multiple testing: CDKN2A/B rs10811661, OR: 1.26 (1.12-1.43) P = 1.8* 10(-4); CDKAL1 rs10946398, OR: 1.23 (1.09-1.39); P = 7.1* 10(-4), and TCF7L2 rs7903146, OR: 1.61 (1.19-2.18) P = 2.3* 10(-3). Only nominal phenotype associations were observed, notably for rs8050136 in FTO and fasting plasma glucose (P = 0.002), postprandial plasma glucose (P = 0.002), and fasting C-peptide levels (P = 0.006) in the diabetic patients, and with BMI in controls (P = 0.033). Conclusions/Significance: We have identified significant association between variants in CDKN2A/B, CDKAL1 and TCF7L2, and type 2 diabetes in a Han Chinese cohort, indicating these genes as strong candidates conferring susceptibility to type 2 diabetes across different ethnicities. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
5
issue
2
publisher
Public Library of Science (PLoS)
external identifiers
  • wos:000274442700017
  • scopus:77949346987
  • pmid:20161779
ISSN
1932-6203
DOI
10.1371/journal.pone.0009153
language
English
LU publication?
yes
id
786264bd-1186-475a-869e-046e2839c25a (old id 1568799)
date added to LUP
2016-04-01 13:56:33
date last changed
2024-04-10 12:57:10
@article{786264bd-1186-475a-869e-046e2839c25a,
  abstract     = {{Background: Recent genome-wide association studies (GWASs) have reported several genetic variants to be reproducibly associated with type 2 diabetes. Additional variants have also been detected from a metaanalysis of three GWASs, performed in populations of European ancestry. In the present study, we evaluated the influence of 17 genetic variants from 15 candidate loci, identified in type 2 diabetes GWASs and the metaanalysis, in a Han Chinese cohort. Methodology/Principal Findings: Selected type 2 diabetes-associated genetic variants were genotyped in 1,165 type 2 diabetic patients and 1,136 normoglycemic control individuals of Southern Han Chinese ancestry. The OR for risk of developing type 2 diabetes was calculated using a logistic regression model adjusted for age, sex, and BMI. Genotype-phenotype associations were tested using a multivariate linear regression model. Genetic variants in CDKN2A/B, CDKAL1, TCF7L2, TCF2, MC4R, and PPARG showed a nominal association with type 2 diabetes (P &lt;= 0.05), of whom the three first would stand correction for multiple testing: CDKN2A/B rs10811661, OR: 1.26 (1.12-1.43) P = 1.8* 10(-4); CDKAL1 rs10946398, OR: 1.23 (1.09-1.39); P = 7.1* 10(-4), and TCF7L2 rs7903146, OR: 1.61 (1.19-2.18) P = 2.3* 10(-3). Only nominal phenotype associations were observed, notably for rs8050136 in FTO and fasting plasma glucose (P = 0.002), postprandial plasma glucose (P = 0.002), and fasting C-peptide levels (P = 0.006) in the diabetic patients, and with BMI in controls (P = 0.033). Conclusions/Significance: We have identified significant association between variants in CDKN2A/B, CDKAL1 and TCF7L2, and type 2 diabetes in a Han Chinese cohort, indicating these genes as strong candidates conferring susceptibility to type 2 diabetes across different ethnicities.}},
  author       = {{Wen, Jie and Rönn, Tina and Olsson, Anders H and Yang, Zhen and Lu, Bin and Du, Yieping and Groop, Leif and Ling, Charlotte and Hu, Renming}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{2}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Investigation of Type 2 Diabetes Risk Alleles Support CDKN2A/B, CDKAL1, and TCF7L2 As Susceptibility Genes in a Han Chinese Cohort}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0009153}},
  doi          = {{10.1371/journal.pone.0009153}},
  volume       = {{5}},
  year         = {{2010}},
}