Genetic Variants of IDE-KIF11-HHEX at 10q23.33 Associated with Type 2 Diabetes Risk: A Fine-Mapping Study in Chinese Population

Qian, Yun; Lu, Feng; Dong, Meihua; Lin, Yudi; Li, Huizhang; Chen, Jian; Shen, Chong; Jin, Guangfu; Hu, Zhibin; Shen, Hongbing

doi:10.1371/journal.pone.0035060

Cited by 33 publications

(33 citation statements)

References 31 publications

(44 reference statements)

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“…These studies have confirmed the important role of these transcription factors not only during fetal organogenesis, but also in carbohydrate and lipid metabolism in adolescents as well as in the pathogenesis of diabetes (6,(8)(9)(10). Therefore, polymorphisms in the HHEX and PROX1 genes have been examined in patients with carbohydrate intolerance and diabetes.…”

Section: Discussionmentioning

confidence: 69%

Hematopoietically expressed homeobox (HHEX) gene polymorphism (rs5015480) is associated with increased risk of gestational diabetes mellitus

et al. 2016

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Gestational diabetes mellitus (GDM) is a metabolic disorder that occurs during pregnancy. HHEX and PROX1 are genetic loci associated with diabetes mellitus type 2. HHEX and PROX1 play significant roles in carbohydrate intolerance and diabetes because these transcription factors may be involved in the regulation of insulin secretion and in glucose and lipid metabolism. The aim of this study was to examine the association between HHEX (rs5015480) and PROX1 (rs340874) gene polymorphisms and GDM. This study included 204 pregnant women with GDM and 207 pregnant women with the normal glucose tolerance (NGT). The diagnosis of GDM was based on a 75-g oral glucose tolerance test at 24-28 weeks' gestation. There was a statistically significant prevalence of the HHEX rs5015480 CC genotype and C allele among women with GDM (C vs T allele, p = 0.021, odds ratio OR = 1.40, 95% CI: 1.05-1.87). Statistically significant higher increase of body mass and BMI during pregnancy was found in women with the HHEX rs5015480 CC genotype. The results of our study suggest an association between the HHEX gene rs5015480 polymorphism and risk of GDM. The HHEX gene rs5015480 C allele may be a risk allele of GDM that is associated with increased BMI during pregnancy.

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Section: Discussionmentioning

confidence: 69%

Hematopoietically expressed homeobox (HHEX) gene polymorphism (rs5015480) is associated with increased risk of gestational diabetes mellitus

et al. 2016

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“…On chromosome 10q23.33, genetic variants in HHEX have been established as susceptibility loci for type 2 diabetes[8]. In our previous fine-mapping study[16], we reported that rs7923837 and rs1111875 were independently associated with risk of type 2 diabetes in a Chinese population. Several studies have also investigated the relationship between HHEX polymorphisms and other metabolic diseases.…”

Section: Discussionmentioning

confidence: 86%

Genetic variants at 10q23.33 are associated with plasma lipid levels in a Chinese population

Liu

Qian

et al. 2014

J Biomed Res

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Plasma lipid abnormalities are implicated in the pathogenic process of type 2 diabetes. The IDE-KIF11-HHEX gene cluster on chromosome 10q23.33 has been identified as a susceptibility locus for type 2 diabetes. We hypothesized that genetic variants at 10q23.33 may be associated with plasma lipid concentrations. Seven tagging single nucleotide polymorphisms (SNPs: rs7923837, rs2488075, rs947591, rs11187146, rs5015480, rs4646957 and rs1111875) at 10q23.33 were genotyped in 3,281 subjects from a Han Chinese population, using the TaqMan OpenArray and Sequenom MassARRAY platforms. Multiple linear regression analyses showed that SNP rs7923837 in the 3′-flanking region of HHEX was significantly associated with triglyceride levels (P = 0.019, 0.031 mmol/L average decrease per minor G allele) and that rs2488075 and rs947591 in the downstream region of HHEX were significantly associated with total cholesterol levels (P = 0.041, 0.058 mmol/L average decrease per minor C allele and P = 0.018, 0.063 mmol/L average decrease per minor A allele, respectively). However, the other four SNPs (rs11187146, rs5015480, rs4646957 and rs1111875) were not significantly associated with any plasma lipid concentrations in this Chinese population. Our data suggest that genetic variants in the IDE-KIF11-HHEX gene cluster at 10q23.33 may partially explain the variation of plasma lipid levels in the Han Chinese population. Further studies are required to confirm these findings in other populations.

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“…One study [24] investigated T2DM risk from both cross-sectional and longitudinal perspectives. Finally, this meta-analysis consisted of 56 cross-sectional studies [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][26][27][28][29][30][31][32][33][34][35][36][37][38][39]41,[43][44][45][48][49][50][51][52][53][55][56][57][58][59][60][63][64]…”

Section: Eligible Studiesmentioning

confidence: 99%

“…Approximately half of included studies (28 studies) [8,9,[11][12][13]15,16,18,21,23,26,29,39,45,48,50,52,[54][55][56][57][58][61][62][63][64][65][66] used less than three SNPs. Twenty-three studies [5,11,15,17,19,20,22,24,27,30,33,37,40,42,46 Figure 1 shows the relationship between the ΔRA total and the crude OR in log scale for T2DM. The slope of log OR for T2DM became less steep at five or more ΔRA total as the ΔRA total increased.…”

Section: Eligible Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Meta‐analytic research on the relationship between cumulative risk alleles and risk of type 2 diabetes mellitus

Kodama

Fujihara

Ishiguro

et al. 2015

Diabetes Metabolism Res

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Genetic Variants of IDE-KIF11-HHEX at 10q23.33 Associated with Type 2 Diabetes Risk: A Fine-Mapping Study in Chinese Population

Cited by 33 publications

References 31 publications

Hematopoietically expressed homeobox (HHEX) gene polymorphism (rs5015480) is associated with increased risk of gestational diabetes mellitus

Hematopoietically expressed homeobox (HHEX) gene polymorphism (rs5015480) is associated with increased risk of gestational diabetes mellitus

Genetic variants at 10q23.33 are associated with plasma lipid levels in a Chinese population

Meta‐analytic research on the relationship between cumulative risk alleles and risk of type 2 diabetes mellitus

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