Polymorphisms in the IDE-KIF11-HHEX Gene Locus Are Reproducibly Associated with Type 2 Diabetes in a Japanese Population

Furukawa, Yasushi; Shimada, Takeshi; Furuta, Hiroto; Matsuno, Shohei; Kusuyama, Akiko; Doi, Asako; Nishi, Masahiro; Sasaki, Hideyuki; Sanke, Tokio; Nanjo, Kishio

doi:10.1210/jc.2007-1029

Cited by 55 publications

(27 citation statements)

References 20 publications

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“…The rs13266634, rs10811661 and rs2237892 risk alleles were major alleles, while the other risk alleles were minor alleles in our population, consistent with previous reports in European populations (Scott et al 2007;Saxena et al 2007;Zeggini et al 2007). Interestingly, the G allele of rs1111875, which was reported to be a major allele in Caucasian ethnic groups, was revealed as a minor allele in our study; this is supported by similar results from Japanese populations (Furukawa et al 2008;Horikoshi et al 2007;Omori et al 2008).…”

Section: Resultssupporting

confidence: 91%

“…In our study, each SNP in the HHEX, CDKN2A/B, CDKAL1 and KCNQ1 genes showed a significant association with T2DM. The adjusted allele-specific OR value of rs1111875 (1.43) was similar to that of Japanese groups (1.30-1.42) (Furukawa et al 2008;Horikoshi et al 2007;Omori et al 2008), but higher than that reported from white populations (1.10-1.15) (Saxena et al 2007;Scott et al 2007;Sladek et al 2007). The HHEX gene product is known to act as both a transcription activator and repressor required for the development of the pancreas, liver and blood vessels and is also a target of the Wnt/b-catenin signaling pathway (McLin et al 2007;Foley and Mercola 2005).…”

Section: Discussionsupporting

confidence: 70%

“…Nevertheless, the effects of genetic variants on the risk of T2DM are somewhat inconsistent among different ethnic groups. For example, Furukawa et al (2008) reported a nominal association between rs13266634, a nonsynonymous SNP in SLC30A8, and T2DM in a Japanese population, while Horikoshi et al (2007) reported that there was no significant association in another Japanese population.…”

Section: Discussionmentioning

confidence: 99%

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Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population

et al. 2008

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According to recent genome-wide association studies, a number of single nucleotide polymorphisms (SNPs) are reported to be associated with type 2 diabetes mellitus (T2DM). The aim of the present study was to investigate the association among the polymorphisms of SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1 and KCNQ1 and the risk of T2DM in the Korean population. This study was based on a multicenter casecontrol study, including 908 patients with T2DM and 502 non-diabetic controls. We genotyped rs13266634, rs1111875, rs10811661, rs4402960, rs8050136, rs734312, rs7754840 and rs2237892 and measured the body weight, body mass index and fasting plasma glucose in all patients and controls. The strongest association was found in a variant of CDKAL1 [rs7754840, odds ratio (OR) = 1.77, 95% CI = 1.50-2.10, p = 5.0 9 10-11 ]. The G allele of rs1111875 (OR = 1.43, 95% CI = 1.18-1.72, p = 1.8 9 10 -4 ) in HHEX), the T allele of rs10811661 (OR = 1.47, 95% CI = 1.23-1.75, p = 2.1 9 10 -5 ) in CDKN2A/B) and the C allele of rs2237892 (OR = 1.31, 95% CI = 1.10-1.56, p = 0.003) in KCNQ1 showed significant associations with T2DM. Rs13266634 (OR = 1.19, 95% CI = 1.00-1.42, p = 0.045) in SLC30A8 showed a nominal association with the risk of T2DM, whereas SNPs in IGF2BP2, FTO and WFS1 were not associated. In conclusion, we have shown that SNPs in HHEX, CDKN2A/B, CDKAL1, KCNQ1 and SLC30A8 confer a risk of T2DM in the Korean population.

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Section: Resultssupporting

confidence: 91%

Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

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Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population

et al. 2008

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“…In addition, Japanese research groups, including ours, recently identified an association of the potassium voltage-gated channel KQT-like subfamily member 1 (KCNQ1) locus with type 2 diabetes in populations of East Asian descent [8,9]. Because most of these loci have also been shown to be associated with type 2 diabetes in other ethnic populations [8][9][10][11][12][13], these loci could be considered as convincing susceptibility genes for type 2 diabetes across different ethnicities.…”

Section: Introductionmentioning

confidence: 93%

Replication study for the association of new meta-analysis-derived risk loci with susceptibility to type 2 diabetes in 6,244 Japanese individuals

et al. 2009

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Aims/hypothesis Additional susceptibility loci for type 2 diabetes have been identified by a meta-analysis of genome-wide association studies (GWASs) in European populations. To examine further the roles of these new loci, we performed a replication study for the association of these single-nucleotide polymorphism (SNP) loci with the disease in three independent Japanese populations. Methods We genotyped seven of the 11 SNPs that emerged in stage 2 of the meta-analysis for European GWASs (rs864745 in JAZF1, rs12779790 near CDC123/CAMK1D, rs7961581 near TSPAN8/LGR5, rs4607103 near ADAMTS9, rs10923931 in NOTCH2, rs1153188 near DCD and rs9472138 near VEGFA) for three independent Japanese populations (first set, 1,630 type 2 diabetes patients vs 1,064 controls; second set, 1,272 type 2 diabetes patients vs 856 controls; third set, 486 type 2 diabetes patients vs 936 controls) using a TaqMan assay. The association of the SNP loci in each population was analysed using a logistic regression analysis, adjusting for age, sex and BMI, and the data were evaluated by a meta-analysis. Results A meta-analysis for the three case-control studies identified a nominal association of rs864745 in JAZF1 with type 2 diabetes (OR 1.148, 95% CI 1.034-1.275, p= Diabetologia

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“…[1][2][3][4][5] TCF7L2, CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8 and HHEX have been widely replicated as susceptibility genes for type 2 diabetes in Asian populations [6][7][8][9][10][11][12] as well as in populations of European ancestry. 13,14 We recently identified KCNQ1 as a novel susceptibility gene, as well as seven other candidate susceptibility loci in a multistage GWAS for type 2 diabetes in the Japanese population, in which a total of 1612 cases and 1424 controls and 100 000 single nucleotide polymorphisms (SNPs) were included.…”

Section: Introductionmentioning

confidence: 99%

Construction of a prediction model for type 2 diabetes mellitus in the Japanese population based on 11 genes with strong evidence of the association

et al. 2009

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Prediction of the disease status is one of the most important objectives of genetic studies. To select the genes with strong evidence of the association with type 2 diabetes mellitus, we validated the associations of the seven candidate loci extracted in our earlier study by genotyping the samples in two independent sample panels. However, except for KCNQ1, the association of none of the remaining seven loci was replicated. We then selected 11 genes, KCNQ1, TCF7L2, CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, HHEX, GCKR, HNF1B, KCNJ11 and PPARG, whose associations with diabetes have already been reported and replicated either in the literature or in this study in the Japanese population. As no evidence of the gene-gene interaction for any pair of the 11 loci was shown, we constructed a prediction model for the disease using the logistic regression analysis by incorporating the number of the risk alleles for the 11 genes, as well as age, sex and body mass index as independent variables. Cumulative risk assessment showed that the addition of one risk allele resulted in an average increase in the odds for the disease of 1.29 (95% CI¼1.25-1.33, P¼5.4Â10 À53 ). The area under the receiver operating characteristic curve, an estimate of the power of the prediction model, was 0.72, thereby indicating that our prediction model for type 2 diabetes may not be so useful but has some value. Incorporation of data from additional risk loci is most likely to increase the predictive power.

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Polymorphisms in the IDE-KIF11-HHEX Gene Locus Are Reproducibly Associated with Type 2 Diabetes in a Japanese Population

Abstract: Polymorphisms in the IDE-KIF11-HHEX gene locus are associated with susceptibility to type 2 diabetes across the boundary of race.

Cited by 55 publications

References 20 publications

Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population

Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population

Replication study for the association of new meta-analysis-derived risk loci with susceptibility to type 2 diabetes in 6,244 Japanese individuals

Construction of a prediction model for type 2 diabetes mellitus in the Japanese population based on 11 genes with strong evidence of the association

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