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Common Variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE Genes Are Associated With Type 2 Diabetes and Impaired Fasting Glucose in a Chinese Han Population
OBJECTIVE— Genome-wide association studies have identified common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, HHEX/IDE, EXT2, and LOC387761 loci that significantly increase the risk of type 2 diabetes. We aimed to replicate these observations in a population-based cohort of Chinese Hans and exam...
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Formato: | Texto |
Lenguaje: | English |
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American Diabetes Association
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551696/ https://www.ncbi.nlm.nih.gov/pubmed/18633108 http://dx.doi.org/10.2337/db08-0047 |
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author | Wu, Ying Li, Huaixing Loos, Ruth J.F. Yu, Zhijie Ye, Xingwang Chen, Lihua Pan, An Hu, Frank B. Lin, Xu |
author_facet | Wu, Ying Li, Huaixing Loos, Ruth J.F. Yu, Zhijie Ye, Xingwang Chen, Lihua Pan, An Hu, Frank B. Lin, Xu |
author_sort | Wu, Ying |
collection | PubMed |
description | OBJECTIVE— Genome-wide association studies have identified common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, HHEX/IDE, EXT2, and LOC387761 loci that significantly increase the risk of type 2 diabetes. We aimed to replicate these observations in a population-based cohort of Chinese Hans and examine the associations of these variants with type 2 diabetes and diabetes-related phenotypes. RESEARCH DESIGN AND METHODS— We genotyped 17 single nucleotide polymorhisms (SNPs) in 3,210 unrelated Chinese Hans, including 424 participants with type 2 diabetes, 878 with impaired fasting glucose (IFG), and 1,908 with normal fasting glucose. RESULTS— We confirmed the associations between type 2 diabetes and variants near CDKAL1 (odds ratio 1.49 [95% CI 1.27–1.75]; P = 8.91 × 10(−7)) and CDKN2A/B (1.31 [1.12–1.54]; P = 1.0 × 10(−3)). We observed significant association of SNPs in IGF2BP2 (1.17 [1.03–1.32]; P = 0.014) and SLC30A8 (1.12 [1.01–1.25]; P = 0.033) with combined IFG/type 2 diabetes. The SNPs in CDKAL1, IGF2BP2, and SLC30A8 were also associated with impaired β-cell function estimated by homeostasis model assessment of β-cell function. When combined, each additional risk allele from CDKAL1-rs9465871, CDKN2A/B-rs10811661, IGF2BP2-rs4402960, and SLC30A8-rs13266634 increased the risk for type 2 diabetes by 1.24-fold (P = 2.85 × 10(−7)) or for combined IFG/type 2 diabetes by 1.21-fold (P = 6.31 × 10(−11)). None of the SNPs in EXT2 or LOC387761 exhibited significant association with type 2 diabetes or IFG. Significant association was observed between the HHEX/IDE SNPs and type 2 diabetes in individuals from Shanghai only (P < 0.013) but not in those from Beijing (P > 0.33). CONCLUSIONS— Our results indicate that in Chinese Hans, common variants in CDKAL1, CDKN2A/B, IGF2BP2, and SLC30A8 loci independently or additively contribute to type 2 diabetes risk, likely mediated through β-cell dysfunction. |
format | Text |
id | pubmed-2551696 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-25516962009-10-01 Common Variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE Genes Are Associated With Type 2 Diabetes and Impaired Fasting Glucose in a Chinese Han Population Wu, Ying Li, Huaixing Loos, Ruth J.F. Yu, Zhijie Ye, Xingwang Chen, Lihua Pan, An Hu, Frank B. Lin, Xu Diabetes Genetics OBJECTIVE— Genome-wide association studies have identified common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, HHEX/IDE, EXT2, and LOC387761 loci that significantly increase the risk of type 2 diabetes. We aimed to replicate these observations in a population-based cohort of Chinese Hans and examine the associations of these variants with type 2 diabetes and diabetes-related phenotypes. RESEARCH DESIGN AND METHODS— We genotyped 17 single nucleotide polymorhisms (SNPs) in 3,210 unrelated Chinese Hans, including 424 participants with type 2 diabetes, 878 with impaired fasting glucose (IFG), and 1,908 with normal fasting glucose. RESULTS— We confirmed the associations between type 2 diabetes and variants near CDKAL1 (odds ratio 1.49 [95% CI 1.27–1.75]; P = 8.91 × 10(−7)) and CDKN2A/B (1.31 [1.12–1.54]; P = 1.0 × 10(−3)). We observed significant association of SNPs in IGF2BP2 (1.17 [1.03–1.32]; P = 0.014) and SLC30A8 (1.12 [1.01–1.25]; P = 0.033) with combined IFG/type 2 diabetes. The SNPs in CDKAL1, IGF2BP2, and SLC30A8 were also associated with impaired β-cell function estimated by homeostasis model assessment of β-cell function. When combined, each additional risk allele from CDKAL1-rs9465871, CDKN2A/B-rs10811661, IGF2BP2-rs4402960, and SLC30A8-rs13266634 increased the risk for type 2 diabetes by 1.24-fold (P = 2.85 × 10(−7)) or for combined IFG/type 2 diabetes by 1.21-fold (P = 6.31 × 10(−11)). None of the SNPs in EXT2 or LOC387761 exhibited significant association with type 2 diabetes or IFG. Significant association was observed between the HHEX/IDE SNPs and type 2 diabetes in individuals from Shanghai only (P < 0.013) but not in those from Beijing (P > 0.33). CONCLUSIONS— Our results indicate that in Chinese Hans, common variants in CDKAL1, CDKN2A/B, IGF2BP2, and SLC30A8 loci independently or additively contribute to type 2 diabetes risk, likely mediated through β-cell dysfunction. American Diabetes Association 2008-10 /pmc/articles/PMC2551696/ /pubmed/18633108 http://dx.doi.org/10.2337/db08-0047 Text en Copyright © 2008, American Diabetes Association https://creativecommons.org/licenses/by-nc-nd/3.0/Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Genetics Wu, Ying Li, Huaixing Loos, Ruth J.F. Yu, Zhijie Ye, Xingwang Chen, Lihua Pan, An Hu, Frank B. Lin, Xu Common Variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE Genes Are Associated With Type 2 Diabetes and Impaired Fasting Glucose in a Chinese Han Population |
title | Common Variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE Genes Are Associated With Type 2 Diabetes and Impaired Fasting Glucose in a Chinese Han Population |
title_full | Common Variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE Genes Are Associated With Type 2 Diabetes and Impaired Fasting Glucose in a Chinese Han Population |
title_fullStr | Common Variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE Genes Are Associated With Type 2 Diabetes and Impaired Fasting Glucose in a Chinese Han Population |
title_full_unstemmed | Common Variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE Genes Are Associated With Type 2 Diabetes and Impaired Fasting Glucose in a Chinese Han Population |
title_short | Common Variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE Genes Are Associated With Type 2 Diabetes and Impaired Fasting Glucose in a Chinese Han Population |
title_sort | common variants in cdkal1, cdkn2a/b, igf2bp2, slc30a8, and hhex/ide genes are associated with type 2 diabetes and impaired fasting glucose in a chinese han population |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551696/ https://www.ncbi.nlm.nih.gov/pubmed/18633108 http://dx.doi.org/10.2337/db08-0047 |
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