Human Molecular Genetics Advance Access originally published online on June 25, 2009
Human Molecular Genetics 2009 18(18):3508-3515; doi:10.1093/hmg/ddp294
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Common variants in KCNQ1 are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population
1 Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China, 2 MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK and 3 Department of Nutrition, Harvard School of Public Health, Boston, MA, USA
* To whom correspondence should be addressed at: Institute for Nutritional Sciences, 294 Tai-Yuan Rd., Shanghai, 200031, China. Tel: +86 2154920249; Fax: +86 2154920249; Email: lihx{at}sibs.ac.cn (H.L.) and xlin{at}sibs.ac.cn (X.L.)
Received April 19, 2009; Revised May 22, 2009; Accepted June 22, 2009
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 x 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.