TY - JOUR
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
N1 - Funding Information:
This study was funded by the research grants from the Chief Scientist Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (SIBS2008006), the National Natural Science Foundation of China (30571562), grant of 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), Major Projects of Knowledge Innovation Program (KSCX2-YW-R-116 and KSCX1-YW-02), and the Shanghai-Unilever Research Development Fund (CH-2006-0941).
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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U2 - 10.1093/hmg/ddp294
DO - 10.1093/hmg/ddp294
M3 - Article
C2 - 19556355
AN - SCOPUS:69449108010
SN - 0964-6906
VL - 18
SP - 3508
EP - 3515
JO - Human molecular genetics
JF - Human molecular genetics
IS - 18
ER -