Association of GCKR rs780094, alone or in combination with GCK rs1799884, with type 2 diabetes and related traits in a Han Chinese population

Q. Qi; Y. Wu; H. Li; R. J.F. Loos; F. B. Hu; L. Sun; L. Lu; A. Pan; C. Liu; H. Wu; L. Chen; Z. Yu; X. Lin

doi:10.1007/s00125-009-1290-2

Association of GCKR rs780094, alone or in combination with GCK rs1799884, with type 2 diabetes and related traits in a Han Chinese population

Q. Qi, Y. Wu, H. Li, R. J.F. Loos, F. B. Hu, L. Sun, L. Lu, A. Pan, C. Liu, H. Wu, L. Chen, Z. Yu, X. Lin

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Abstract

Aims/hypothesis: The GCKR rs780094 and GCK rs1799884 polymorphisms have been reported to be associated with dyslipidaemia and type 2 diabetes in white Europeans. The aim of this study was to replicate these associations in Han Chinese individuals and to identify the potential mechanisms underlying these associations. Methods: The single nucleotide polymorphisms rs780094 and rs1799884 were genotyped in a population-based sample of Han Chinese individuals (n∈=∈3,210) and tested for association with risk of type 2 diabetes and related phenotypes. Results: The GCKR rs780094 A allele was marginally associated with reduced risk of type 2 diabetes (OR 0.85, 95% CI 0.73-1.00, p value under an additive model [p _(add)]∈=∈0.05) and significantly associated with reduced risk of impaired fasting glucose (IFG) or type 2 diabetes (OR 0.86, 95% CI 0.77-0.96, p _[add]∈=∈0. 0032). It was also significantly associated with decreased fasting glucose and increased HOMA of beta cell function (HOMA-B) and fasting triacylglycerol levels (p _[add]∈=∈0.0169-5.3∈×∈10^-6), but not with HOMA of insulin sensitivity (HOMA-S). The associations with type 2 diabetes and IFG remained significant after adjustment for BMI, while adjustment for HOMA-B abolished the associations. The GCKR rs780094 was also associated with obesity and BMI, independently of its association with type 2 diabetes. The GCK rs1799884 A allele was significantly associated with decreased HOMA-B (p _[add]∈=∈0.0005), but not with type 2 diabetes or IFG. Individuals with increasing numbers of risk alleles for both variants had significantly lower HOMA-B (p _[add]∈=∈5. 8∈×∈10^-5) in the combined analysis. Conclusions/interpretation: Consistent with observations in white Europeans, the GCKR rs780094 polymorphism contributes to the risk of type 2 diabetes and dyslipidaemia in Han Chinese individuals. In addition, we showed that the effect on type 2 diabetes is probably mediated through impaired beta cell function rather than through obesity.

Original language	English
Pages (from-to)	834-843
Number of pages	10
Journal	Diabetologia
Volume	52
Issue number	5
DOIs	https://doi.org/10.1007/s00125-009-1290-2
Publication status	Published - May 2009
Externally published	Yes

Bibliographical note

Funding Information:
Acknowledgements This study was funded by research grants from the National Natural Science Foundation of China (30571562), the Knowledge Innovation Program Pilot Project of the Chinese Academy of Sciences (KSCX2-YW-R-73), the National Basic Research Program of China (973 Program 2006CB503902), the Major Projects of Knowledge Innovation Program (KSCX2-YW-R-116 and KSCX1-YW-02) and the Shanghai-Unilever Research Development Fund (CH-2006-0941). We are grateful to all those who participated in the Nutrition and Health of Aging Population in China study. We also thank X. Pang, Z. Zhang, S. Jiao, H. Liu and S. Zou from the Beijing and Shanghai Centers for Disease Control and Prevention for participating in the field work, and our colleagues X. Ye and J. Wang from the Institute for Nutritional Sciences for their part in the laboratory analyses.

ASJC Scopus Subject Areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s00125-009-1290-2

Cite this

@article{959d58bf80e145e599ab31e04bf9f8b0,

title = "Association of GCKR rs780094, alone or in combination with GCK rs1799884, with type 2 diabetes and related traits in a Han Chinese population",

abstract = "Aims/hypothesis: The GCKR rs780094 and GCK rs1799884 polymorphisms have been reported to be associated with dyslipidaemia and type 2 diabetes in white Europeans. The aim of this study was to replicate these associations in Han Chinese individuals and to identify the potential mechanisms underlying these associations. Methods: The single nucleotide polymorphisms rs780094 and rs1799884 were genotyped in a population-based sample of Han Chinese individuals (n∈=∈3,210) and tested for association with risk of type 2 diabetes and related phenotypes. Results: The GCKR rs780094 A allele was marginally associated with reduced risk of type 2 diabetes (OR 0.85, 95% CI 0.73-1.00, p value under an additive model [p (add)]∈=∈0.05) and significantly associated with reduced risk of impaired fasting glucose (IFG) or type 2 diabetes (OR 0.86, 95% CI 0.77-0.96, p [add]∈=∈0. 0032). It was also significantly associated with decreased fasting glucose and increased HOMA of beta cell function (HOMA-B) and fasting triacylglycerol levels (p [add]∈=∈0.0169-5.3∈×∈10-6), but not with HOMA of insulin sensitivity (HOMA-S). The associations with type 2 diabetes and IFG remained significant after adjustment for BMI, while adjustment for HOMA-B abolished the associations. The GCKR rs780094 was also associated with obesity and BMI, independently of its association with type 2 diabetes. The GCK rs1799884 A allele was significantly associated with decreased HOMA-B (p [add]∈=∈0.0005), but not with type 2 diabetes or IFG. Individuals with increasing numbers of risk alleles for both variants had significantly lower HOMA-B (p [add]∈=∈5. 8∈×∈10-5) in the combined analysis. Conclusions/interpretation: Consistent with observations in white Europeans, the GCKR rs780094 polymorphism contributes to the risk of type 2 diabetes and dyslipidaemia in Han Chinese individuals. In addition, we showed that the effect on type 2 diabetes is probably mediated through impaired beta cell function rather than through obesity.",

author = "Q. Qi and Y. Wu and H. Li and Loos, {R. J.F.} and Hu, {F. B.} and L. Sun and L. Lu and A. Pan and C. Liu and H. Wu and L. Chen and Z. Yu and X. Lin",

note = "Funding Information: Acknowledgements This study was funded by research grants from the National Natural Science Foundation of China (30571562), the Knowledge Innovation Program Pilot Project of the Chinese Academy of Sciences (KSCX2-YW-R-73), the National Basic Research Program of China (973 Program 2006CB503902), the Major Projects of Knowledge Innovation Program (KSCX2-YW-R-116 and KSCX1-YW-02) and the Shanghai-Unilever Research Development Fund (CH-2006-0941). We are grateful to all those who participated in the Nutrition and Health of Aging Population in China study. We also thank X. Pang, Z. Zhang, S. Jiao, H. Liu and S. Zou from the Beijing and Shanghai Centers for Disease Control and Prevention for participating in the field work, and our colleagues X. Ye and J. Wang from the Institute for Nutritional Sciences for their part in the laboratory analyses.",

year = "2009",

month = may,

doi = "10.1007/s00125-009-1290-2",

language = "English",

volume = "52",

pages = "834--843",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer Verlag",

number = "5",

}

TY - JOUR

T1 - Association of GCKR rs780094, alone or in combination with GCK rs1799884, with type 2 diabetes and related traits in a Han Chinese population

AU - Qi, Q.

AU - Wu, Y.

AU - Li, H.

AU - Loos, R. J.F.

AU - Hu, F. B.

AU - Sun, L.

AU - Lu, L.

AU - Pan, A.

AU - Liu, C.

AU - Wu, H.

AU - Chen, L.

AU - Yu, Z.

AU - Lin, X.

N1 - Funding Information: Acknowledgements This study was funded by research grants from the National Natural Science Foundation of China (30571562), the Knowledge Innovation Program Pilot Project of the Chinese Academy of Sciences (KSCX2-YW-R-73), the National Basic Research Program of China (973 Program 2006CB503902), the Major Projects of Knowledge Innovation Program (KSCX2-YW-R-116 and KSCX1-YW-02) and the Shanghai-Unilever Research Development Fund (CH-2006-0941). We are grateful to all those who participated in the Nutrition and Health of Aging Population in China study. We also thank X. Pang, Z. Zhang, S. Jiao, H. Liu and S. Zou from the Beijing and Shanghai Centers for Disease Control and Prevention for participating in the field work, and our colleagues X. Ye and J. Wang from the Institute for Nutritional Sciences for their part in the laboratory analyses.

PY - 2009/5

Y1 - 2009/5

N2 - Aims/hypothesis: The GCKR rs780094 and GCK rs1799884 polymorphisms have been reported to be associated with dyslipidaemia and type 2 diabetes in white Europeans. The aim of this study was to replicate these associations in Han Chinese individuals and to identify the potential mechanisms underlying these associations. Methods: The single nucleotide polymorphisms rs780094 and rs1799884 were genotyped in a population-based sample of Han Chinese individuals (n∈=∈3,210) and tested for association with risk of type 2 diabetes and related phenotypes. Results: The GCKR rs780094 A allele was marginally associated with reduced risk of type 2 diabetes (OR 0.85, 95% CI 0.73-1.00, p value under an additive model [p (add)]∈=∈0.05) and significantly associated with reduced risk of impaired fasting glucose (IFG) or type 2 diabetes (OR 0.86, 95% CI 0.77-0.96, p [add]∈=∈0. 0032). It was also significantly associated with decreased fasting glucose and increased HOMA of beta cell function (HOMA-B) and fasting triacylglycerol levels (p [add]∈=∈0.0169-5.3∈×∈10-6), but not with HOMA of insulin sensitivity (HOMA-S). The associations with type 2 diabetes and IFG remained significant after adjustment for BMI, while adjustment for HOMA-B abolished the associations. The GCKR rs780094 was also associated with obesity and BMI, independently of its association with type 2 diabetes. The GCK rs1799884 A allele was significantly associated with decreased HOMA-B (p [add]∈=∈0.0005), but not with type 2 diabetes or IFG. Individuals with increasing numbers of risk alleles for both variants had significantly lower HOMA-B (p [add]∈=∈5. 8∈×∈10-5) in the combined analysis. Conclusions/interpretation: Consistent with observations in white Europeans, the GCKR rs780094 polymorphism contributes to the risk of type 2 diabetes and dyslipidaemia in Han Chinese individuals. In addition, we showed that the effect on type 2 diabetes is probably mediated through impaired beta cell function rather than through obesity.

AB - Aims/hypothesis: The GCKR rs780094 and GCK rs1799884 polymorphisms have been reported to be associated with dyslipidaemia and type 2 diabetes in white Europeans. The aim of this study was to replicate these associations in Han Chinese individuals and to identify the potential mechanisms underlying these associations. Methods: The single nucleotide polymorphisms rs780094 and rs1799884 were genotyped in a population-based sample of Han Chinese individuals (n∈=∈3,210) and tested for association with risk of type 2 diabetes and related phenotypes. Results: The GCKR rs780094 A allele was marginally associated with reduced risk of type 2 diabetes (OR 0.85, 95% CI 0.73-1.00, p value under an additive model [p (add)]∈=∈0.05) and significantly associated with reduced risk of impaired fasting glucose (IFG) or type 2 diabetes (OR 0.86, 95% CI 0.77-0.96, p [add]∈=∈0. 0032). It was also significantly associated with decreased fasting glucose and increased HOMA of beta cell function (HOMA-B) and fasting triacylglycerol levels (p [add]∈=∈0.0169-5.3∈×∈10-6), but not with HOMA of insulin sensitivity (HOMA-S). The associations with type 2 diabetes and IFG remained significant after adjustment for BMI, while adjustment for HOMA-B abolished the associations. The GCKR rs780094 was also associated with obesity and BMI, independently of its association with type 2 diabetes. The GCK rs1799884 A allele was significantly associated with decreased HOMA-B (p [add]∈=∈0.0005), but not with type 2 diabetes or IFG. Individuals with increasing numbers of risk alleles for both variants had significantly lower HOMA-B (p [add]∈=∈5. 8∈×∈10-5) in the combined analysis. Conclusions/interpretation: Consistent with observations in white Europeans, the GCKR rs780094 polymorphism contributes to the risk of type 2 diabetes and dyslipidaemia in Han Chinese individuals. In addition, we showed that the effect on type 2 diabetes is probably mediated through impaired beta cell function rather than through obesity.

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Association of GCKR rs780094, alone or in combination with GCK rs1799884, with type 2 diabetes and related traits in a Han Chinese population

Abstract

Bibliographical note

ASJC Scopus Subject Areas

PubMed: MeSH publication types

UN SDGs

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