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

Qibin 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

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Pages (from-to)834-843
Number of pages10
JournalDiabetologia
Volume52
Issue number5
DOIs
StatePublished - May 2009
Externally publishedYes

Fingerprint

Type 2 Diabetes Mellitus
Fasting
Population
Glucose
Alleles
Dyslipidemias
Obesity
Single Nucleotide Polymorphism
Insulin Resistance
Triglycerides
Phenotype

Keywords

  • Association study
  • Chinese
  • GCK
  • GCKR
  • Obesity
  • Type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Association of GCKR rs780094, alone or in combination with GCK rs1799884, with type 2 diabetes and related traits in a Han Chinese population. / Qi, Qibin; Wu, Y.; Li, H.; Loos, R. J F; Hu, F. B.; Sun, L.; Lu, L.; Pan, A.; Liu, C.; Wu, H.; Chen, L.; Yu, Z.; Lin, X.

In: Diabetologia, Vol. 52, No. 5, 05.2009, p. 834-843.

Research output: Contribution to journalArticle

Qi, Q, Wu, Y, Li, H, Loos, RJF, Hu, FB, Sun, L, Lu, L, Pan, A, Liu, C, Wu, H, Chen, L, Yu, Z & Lin, X 2009, 'Association of GCKR rs780094, alone or in combination with GCK rs1799884, with type 2 diabetes and related traits in a Han Chinese population', Diabetologia, vol. 52, no. 5, pp. 834-843. https://doi.org/10.1007/s00125-009-1290-2
Qi, Qibin ; Wu, Y. ; Li, H. ; Loos, R. J F ; Hu, F. B. ; Sun, L. ; Lu, L. ; Pan, A. ; Liu, C. ; Wu, H. ; Chen, L. ; Yu, Z. ; Lin, X. / Association of GCKR rs780094, alone or in combination with GCK rs1799884, with type 2 diabetes and related traits in a Han Chinese population. In: Diabetologia. 2009 ; Vol. 52, No. 5. pp. 834-843.
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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.",
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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, Qibin

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.

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.

KW - Association study

KW - Chinese

KW - GCK

KW - GCKR

KW - Obesity

KW - Type 2 diabetes

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