Genetic variants on chromosome 6p21.1 and 6p22.3 are associated with type 2 diabetes risk: a case–control study in Han Chinese

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

doi:10.1038/jhg.2012.25

Cited by 26 publications

(15 citation statements)

References 35 publications

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“…Two studies deviating from the Hardy-Weinberg equilibrium (HWE) were rejected. All of information was extracted from 26,120 T2DM cases and 36,447 controls (Table 1)69101112131415161718192021. One publication generally included one study.…”

Section: Resultsmentioning

confidence: 99%

CDKAL1 gene rs7756992 A/G polymorphism and type 2 diabetes mellitus: a meta-analysis of 62,567 subjects

Wang

et al. 2013

Sci Rep

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The Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like (CDKAL1) gene rs7756992 A/G polymorphism has been suggested to be associated with type 2 diabetes mellitus (T2DM), but the individual studies results are still controversial. To explore the association of CDKAL1 gene rs7756992 A/G polymorphism with T2DM, a meta-analysis involving 62,567 subjects from 21 separate studies was conducted. In the whole population, a significant association was found between CDKAL1 gene rs7756992 A/G polymorphism and T2DM under allelic (OR: 1.180, 95% CI: 1.130–1.230, P = 1.60 × 10−14), recessive (OR: 1.510, 95% CI: 1.380–1.660, P = 8.41 × 10−18), dominant (OR: 1.175, 95% CI: 1.109–1.246, P = 6.30 × 10−8), homozygous (OR: 1.400, 95% CI: 1.282–1.530, P = 8.02 × 10−14), and heterozygous genetic models (OR: 1.101, 95% CI: 1.040–1.166, P = 0.001). CDKAL1 gene rs7756992 A/G polymorphism was significantly associated with T2DM. The person with G allele of CDKAL1 gene rs7756992 A/G polymorphism might be predisposed to T2DM.

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Section: Resultsmentioning

confidence: 99%

CDKAL1 gene rs7756992 A/G polymorphism and type 2 diabetes mellitus: a meta-analysis of 62,567 subjects

Wang

et al. 2013

Sci Rep

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“…Finally, although no direct links between angiogenic factor genetic variants and diabetes have been reported, allelic variants of VEGF (50) and the VEGF-inducer transcription factor hypoxia inducible factor-1α have been described in T2D patients (51). Moreover, polymorphisms in the VEGF-A gene have been reported in patients with micro and macrovascular diabetic secondary complications (52,53).…”

Section: Discussionmentioning

confidence: 99%

Vascular Endothelial Growth Factor–Mediated Islet Hypervascularization and Inflammation Contribute to Progressive Reduction of β-Cell Mass

et al. 2012

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Type 2 diabetes (T2D) results from insulin resistance and inadequate insulin secretion. Insulin resistance initially causes compensatory islet hyperplasia that progresses to islet disorganization and altered vascularization, inflammation, and, finally, decreased functional β-cell mass and hyperglycemia. The precise mechanism(s) underlying β-cell failure remain to be elucidated. In this study, we show that in insulin-resistant high-fat diet-fed mice, the enhanced islet vascularization and inflammation was parallel to an increased expression of vascular endothelial growth factor A (VEGF). To elucidate the role of VEGF in these processes, we have genetically engineered β-cells to overexpress VEGF (in transgenic mice or after adeno-associated viral vector-mediated gene transfer). We found that sustained increases in β-cell VEGF levels led to disorganized, hypervascularized, and fibrotic islets, progressive macrophage infiltration, and proinflammatory cytokine production, including tumor necrosis factor-α and interleukin-1β. This resulted in impaired insulin secretion, decreased β-cell mass, and hyperglycemia with age. These results indicate that sustained VEGF upregulation may participate in the initiation of a process leading to β-cell failure and further suggest that compensatory islet hyperplasia and hypervascularization may contribute to progressive inflammation and β-cell mass loss during T2D.

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“…All subjects were genetically unrelated ethnic Han Chinese and the study population was previously described [22,23]. In brief, 2,925 T2D cases and 3,281 controls were recruited from 2 community-based chronic non-communicable disease surveys in Jiangsu province, from 2004 to 2008.…”

Section: Methodsmentioning

confidence: 99%

Genetic variant in fat mass and obesity-associated gene associated with type 2 diabetes risk in Han Chinese

Qian

Liu

et al. 2013

BMC Genet

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BackgroundGenome-wide association study (GWAS) has identified that rs8050136 C/A polymorphism in fat mass and obesity-associated gene (FTO) was associated with the risk of type 2 diabetes (T2D) in Europeans. But this association was abolished after adjustment for body mass index (BMI), suggesting that the effect of rs8050136 on T2D risk might be mediated by BMI in Europeans. However, the findings in subsequent studies were inconsistent among Asian populations. To determine whether rs8050136 polymorphism in FTO is independently associated with the risk of T2D in Chinese, we conducted a case–control study with 2,925 T2D patients and 3,281 controls in Han Chinese.ResultsLogistic regression revealed that the A allele of rs8050136 was significantly associated with an increased risk of T2D, independent of BMI (odds ratio (OR) = 1.17, 95% confidence interval (95% CI) = 1.03-1.32, p = 0.016). Meta-analysis containing 10 reported studies and our data with a total of 15,819 cases and 18,314 controls further confirmed the association between rs8050136 polymorphism and T2D risk in East Asians (OR = 1.13, 95% CI = 1.07-1.19).ConclusionsOur findings indicate that the genetic variant in FTO may contribute to T2D risk in Han Chinese and rs8050136 polymorphism may be a genetic marker for T2D susceptibility.

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Genetic variants on chromosome 6p21.1 and 6p22.3 are associated with type 2 diabetes risk: a case–control study in Han Chinese

Cited by 26 publications

References 35 publications

CDKAL1 gene rs7756992 A/G polymorphism and type 2 diabetes mellitus: a meta-analysis of 62,567 subjects

CDKAL1 gene rs7756992 A/G polymorphism and type 2 diabetes mellitus: a meta-analysis of 62,567 subjects

Vascular Endothelial Growth Factor–Mediated Islet Hypervascularization and Inflammation Contribute to Progressive Reduction of β-Cell Mass

Genetic variant in fat mass and obesity-associated gene associated with type 2 diabetes risk in Han Chinese

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