Common variants in KCNQ1 are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population

Qibin Qi, Huaixing Li, Ruth J F Loos, Chen Liu, Ying Wu, Frank B. Hu, Hongyu Wu, Ling Lu, Zhijie Yu, Xu Lin

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Abstract

Common variants in KCNQ1 have recently been reported to be associated with type 2 diabetes in East Asians. We aimed to examine whether these common variants (rs2074196, rs2237892, rs2237895 and rs2237897) were also associated with type 2 diabetes in a population-based cohort of 3210 Chinese Hans and to explore the underlying mechanisms. The SNPs rs2237892, rs2237895 and rs2237897 were significantly associated with type 2 diabetes (OR: 1.33-1.36, P ≤ 0.0009), impaired fasting glucose (IFG) (OR: 1.16-1.19, P ≤ 0.0193) and combined IFG/type 2 diabetes (OR: 1.23-1.24, P ≤ 0.0004), and the corresponding population attributable risks of type 2 diabetes for the three SNPs were 32.5, 18.8 and 35.8%, respectively. However, rs2074196 showed a weak, but significant association with IFG (OR: 1.18 [1.04-1.33], P = 0.009) and combined IFG/type 2 diabetes (OR: 1.17 [1.05-1.30], P = 0.0053), as well as a trend toward association with type 2 diabetes (OR: 1.15 [0.98-1.35], P = 0.0882), suggesting a different pattern of association when compared with the other three SNPs. The four SNPs were all significantly associated with HOMA-B (P ≤ 0.042) while rs2237895 and rs22378897 also showed significant association with fasting glucose (P ≤ 0.012). Notably, the associations with type 2 diabetes were markedly attenuated after adjusting for HOMA-B (ORrs2237892: 1.33 [1.05-1.68], P = 0.018; ORrs2237895: 1.24 [1.00-1.54], P = 0.0524; ORrs2237897: 1.22[0.98-1.53], P = 0.09). Moreover, GCCC haplotype showed similar associations with type 2 diabetes (OR: 1.48 [1.17-1.85], P = 0.0008), IFG (OR: 1.32 [1.10-1.57], P = 0.0023), combined IFG/type 2 diabetes (OR: 1.37 [1.17-1.61], P = 8.7 × 10-5), and lower HOMA-B values (β = -4.41 ± 1.62, P = 0.006). These results suggest that KCNQ1 is a major type 2 diabetes gene in the Chinese Hans and it may confer type 2 diabetes risk by impaired β-cell function.

Original languageEnglish (US)
Pages (from-to)3508-3515
Number of pages8
JournalHuman Molecular Genetics
Volume18
Issue number18
DOIs
StatePublished - 2009
Externally publishedYes

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Type 2 Diabetes Mellitus
Fasting
Glucose
Population
Single Nucleotide Polymorphism
Haplotypes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Common variants in KCNQ1 are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population. / Qi, Qibin; Li, Huaixing; Loos, Ruth J F; Liu, Chen; Wu, Ying; Hu, Frank B.; Wu, Hongyu; Lu, Ling; Yu, Zhijie; Lin, Xu.

In: Human Molecular Genetics, Vol. 18, No. 18, 2009, p. 3508-3515.

Research output: Contribution to journalArticle

Qi, Qibin ; Li, Huaixing ; Loos, Ruth J F ; Liu, Chen ; Wu, Ying ; Hu, Frank B. ; Wu, Hongyu ; Lu, Ling ; Yu, Zhijie ; Lin, Xu. / Common variants in KCNQ1 are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population. In: Human Molecular Genetics. 2009 ; Vol. 18, No. 18. pp. 3508-3515.
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title = "Common variants in KCNQ1 are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population",
abstract = "Common variants in KCNQ1 have recently been reported to be associated with type 2 diabetes in East Asians. We aimed to examine whether these common variants (rs2074196, rs2237892, rs2237895 and rs2237897) were also associated with type 2 diabetes in a population-based cohort of 3210 Chinese Hans and to explore the underlying mechanisms. The SNPs rs2237892, rs2237895 and rs2237897 were significantly associated with type 2 diabetes (OR: 1.33-1.36, P ≤ 0.0009), impaired fasting glucose (IFG) (OR: 1.16-1.19, P ≤ 0.0193) and combined IFG/type 2 diabetes (OR: 1.23-1.24, P ≤ 0.0004), and the corresponding population attributable risks of type 2 diabetes for the three SNPs were 32.5, 18.8 and 35.8{\%}, respectively. However, rs2074196 showed a weak, but significant association with IFG (OR: 1.18 [1.04-1.33], P = 0.009) and combined IFG/type 2 diabetes (OR: 1.17 [1.05-1.30], P = 0.0053), as well as a trend toward association with type 2 diabetes (OR: 1.15 [0.98-1.35], P = 0.0882), suggesting a different pattern of association when compared with the other three SNPs. The four SNPs were all significantly associated with HOMA-B (P ≤ 0.042) while rs2237895 and rs22378897 also showed significant association with fasting glucose (P ≤ 0.012). Notably, the associations with type 2 diabetes were markedly attenuated after adjusting for HOMA-B (ORrs2237892: 1.33 [1.05-1.68], P = 0.018; ORrs2237895: 1.24 [1.00-1.54], P = 0.0524; ORrs2237897: 1.22[0.98-1.53], P = 0.09). Moreover, GCCC haplotype showed similar associations with type 2 diabetes (OR: 1.48 [1.17-1.85], P = 0.0008), IFG (OR: 1.32 [1.10-1.57], P = 0.0023), combined IFG/type 2 diabetes (OR: 1.37 [1.17-1.61], P = 8.7 × 10-5), and lower HOMA-B values (β = -4.41 ± 1.62, P = 0.006). These results suggest that KCNQ1 is a major type 2 diabetes gene in the Chinese Hans and it may confer type 2 diabetes risk by impaired β-cell function.",
author = "Qibin Qi and Huaixing Li and Loos, {Ruth J F} and Chen Liu and Ying Wu and Hu, {Frank B.} and Hongyu Wu and Ling Lu and Zhijie Yu and Xu Lin",
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T1 - Common variants in KCNQ1 are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population

AU - Qi, Qibin

AU - Li, Huaixing

AU - Loos, Ruth J F

AU - Liu, Chen

AU - Wu, Ying

AU - Hu, Frank B.

AU - Wu, Hongyu

AU - Lu, Ling

AU - Yu, Zhijie

AU - Lin, Xu

PY - 2009

Y1 - 2009

N2 - Common variants in KCNQ1 have recently been reported to be associated with type 2 diabetes in East Asians. We aimed to examine whether these common variants (rs2074196, rs2237892, rs2237895 and rs2237897) were also associated with type 2 diabetes in a population-based cohort of 3210 Chinese Hans and to explore the underlying mechanisms. The SNPs rs2237892, rs2237895 and rs2237897 were significantly associated with type 2 diabetes (OR: 1.33-1.36, P ≤ 0.0009), impaired fasting glucose (IFG) (OR: 1.16-1.19, P ≤ 0.0193) and combined IFG/type 2 diabetes (OR: 1.23-1.24, P ≤ 0.0004), and the corresponding population attributable risks of type 2 diabetes for the three SNPs were 32.5, 18.8 and 35.8%, respectively. However, rs2074196 showed a weak, but significant association with IFG (OR: 1.18 [1.04-1.33], P = 0.009) and combined IFG/type 2 diabetes (OR: 1.17 [1.05-1.30], P = 0.0053), as well as a trend toward association with type 2 diabetes (OR: 1.15 [0.98-1.35], P = 0.0882), suggesting a different pattern of association when compared with the other three SNPs. The four SNPs were all significantly associated with HOMA-B (P ≤ 0.042) while rs2237895 and rs22378897 also showed significant association with fasting glucose (P ≤ 0.012). Notably, the associations with type 2 diabetes were markedly attenuated after adjusting for HOMA-B (ORrs2237892: 1.33 [1.05-1.68], P = 0.018; ORrs2237895: 1.24 [1.00-1.54], P = 0.0524; ORrs2237897: 1.22[0.98-1.53], P = 0.09). Moreover, GCCC haplotype showed similar associations with type 2 diabetes (OR: 1.48 [1.17-1.85], P = 0.0008), IFG (OR: 1.32 [1.10-1.57], P = 0.0023), combined IFG/type 2 diabetes (OR: 1.37 [1.17-1.61], P = 8.7 × 10-5), and lower HOMA-B values (β = -4.41 ± 1.62, P = 0.006). These results suggest that KCNQ1 is a major type 2 diabetes gene in the Chinese Hans and it may confer type 2 diabetes risk by impaired β-cell function.

AB - Common variants in KCNQ1 have recently been reported to be associated with type 2 diabetes in East Asians. We aimed to examine whether these common variants (rs2074196, rs2237892, rs2237895 and rs2237897) were also associated with type 2 diabetes in a population-based cohort of 3210 Chinese Hans and to explore the underlying mechanisms. The SNPs rs2237892, rs2237895 and rs2237897 were significantly associated with type 2 diabetes (OR: 1.33-1.36, P ≤ 0.0009), impaired fasting glucose (IFG) (OR: 1.16-1.19, P ≤ 0.0193) and combined IFG/type 2 diabetes (OR: 1.23-1.24, P ≤ 0.0004), and the corresponding population attributable risks of type 2 diabetes for the three SNPs were 32.5, 18.8 and 35.8%, respectively. However, rs2074196 showed a weak, but significant association with IFG (OR: 1.18 [1.04-1.33], P = 0.009) and combined IFG/type 2 diabetes (OR: 1.17 [1.05-1.30], P = 0.0053), as well as a trend toward association with type 2 diabetes (OR: 1.15 [0.98-1.35], P = 0.0882), suggesting a different pattern of association when compared with the other three SNPs. The four SNPs were all significantly associated with HOMA-B (P ≤ 0.042) while rs2237895 and rs22378897 also showed significant association with fasting glucose (P ≤ 0.012). Notably, the associations with type 2 diabetes were markedly attenuated after adjusting for HOMA-B (ORrs2237892: 1.33 [1.05-1.68], P = 0.018; ORrs2237895: 1.24 [1.00-1.54], P = 0.0524; ORrs2237897: 1.22[0.98-1.53], P = 0.09). Moreover, GCCC haplotype showed similar associations with type 2 diabetes (OR: 1.48 [1.17-1.85], P = 0.0008), IFG (OR: 1.32 [1.10-1.57], P = 0.0023), combined IFG/type 2 diabetes (OR: 1.37 [1.17-1.61], P = 8.7 × 10-5), and lower HOMA-B values (β = -4.41 ± 1.62, P = 0.006). These results suggest that KCNQ1 is a major type 2 diabetes gene in the Chinese Hans and it may confer type 2 diabetes risk by impaired β-cell function.

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