Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects.

<h4>Background</h4>Previous studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for type 2 diabetes (T2D) acting through elevated...

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Autores principales:	Claudia Ha Ting Tam, Janice Sin Ka Ho, Ying Wang, Heung Man Lee, Vincent Kwok Lim Lam, Soren Germer, Mitchell Martin, Wing Yee So, Ronald Ching Wan Ma, Juliana Chung Ngor Chan, Maggie Chor Yin Ng
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b9fae586310a4eb090493d47f4a01baf
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spelling	oai:doaj.org-article:b9fae586310a4eb090493d47f4a01baf2021-12-02T20:20:15ZCommon polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects.1932-620310.1371/journal.pone.0011428https://doaj.org/article/b9fae586310a4eb090493d47f4a01baf2010-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20628598/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Previous studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for type 2 diabetes (T2D) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with T2D and glucose homeostasis in three independent Chinese cohorts.<h4>Methodology/principal findings</h4>Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 T2D patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with FPG, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with GCKR rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and G6PC2 rs16856187 on FPG.<h4>Conclusions/significance</h4>Common variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals.Claudia Ha Ting TamJanice Sin Ka HoYing WangHeung Man LeeVincent Kwok Lim LamSoren GermerMitchell MartinWing Yee SoRonald Ching Wan MaJuliana Chung Ngor ChanMaggie Chor Yin NgPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 7, p e11428 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Claudia Ha Ting Tam Janice Sin Ka Ho Ying Wang Heung Man Lee Vincent Kwok Lim Lam Soren Germer Mitchell Martin Wing Yee So Ronald Ching Wan Ma Juliana Chung Ngor Chan Maggie Chor Yin Ng Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects.
description	<h4>Background</h4>Previous studies identified melatonin receptor 1B (MTNR1B), islet-specific glucose 6 phosphatase catalytic subunit-related protein (G6PC2), glucokinase (GCK) and glucokinase regulatory protein (GCKR) as candidate genes for type 2 diabetes (T2D) acting through elevated fasting plasma glucose (FPG). We examined the associations of the reported common variants of these genes with T2D and glucose homeostasis in three independent Chinese cohorts.<h4>Methodology/principal findings</h4>Five single nucleotide polymorphisms (SNPs), MTNR1B rs10830963, G6PC2 rs16856187 and rs478333, GCK rs1799884 and GCKR rs780094, were genotyped in 1644 controls (583 adults and 1061 adolescents) and 1342 T2D patients. The G-allele of MTNR1B rs10830963 and the C-alleles of both G6PC2 rs16856187 and rs478333 were associated with higher FPG (0.0034<P<6.6x10(-5)) in healthy controls. In addition to our previous report for association with FPG, the A-allele of GCK rs1799884 was also associated with reduced homeostasis model assessment of beta-cell function (HOMA-B) (P=0.0015). Together with GCKR rs780094, the risk alleles of these SNPs exhibited dosage effect in their associations with increased FPG (P=2.9x10(-9)) and reduced HOMA-B (P=1.1x10(-3)). Meta-analyses strongly supported additive effects of MTNR1B rs10830963 and G6PC2 rs16856187 on FPG.<h4>Conclusions/significance</h4>Common variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals.
format	article
author	Claudia Ha Ting Tam Janice Sin Ka Ho Ying Wang Heung Man Lee Vincent Kwok Lim Lam Soren Germer Mitchell Martin Wing Yee So Ronald Ching Wan Ma Juliana Chung Ngor Chan Maggie Chor Yin Ng
author_facet	Claudia Ha Ting Tam Janice Sin Ka Ho Ying Wang Heung Man Lee Vincent Kwok Lim Lam Soren Germer Mitchell Martin Wing Yee So Ronald Ching Wan Ma Juliana Chung Ngor Chan Maggie Chor Yin Ng
author_sort	Claudia Ha Ting Tam
title	Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects.
title_short	Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects.
title_full	Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects.
title_fullStr	Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects.
title_full_unstemmed	Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects.
title_sort	common polymorphisms in mtnr1b, g6pc2 and gck are associated with increased fasting plasma glucose and impaired beta-cell function in chinese subjects.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/b9fae586310a4eb090493d47f4a01baf
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Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects.

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