KCNQ1 common genetic variant and type 2 diabetes mellitus risk

Erfani, Taraneh; Sarhangi, Negar; Afshari, Mahdi; Abbasi, Davood; Meybodi, Hamid Reza Aghaei; Hasanzad, Mandana

doi:10.1007/s40200-019-00473-4

Cited by 8 publications

(4 citation statements)

References 23 publications

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“…T2DM and decreased insulin secretion were found to be related to these polymorphisms in a variety of groups, including Asians, Europeans, and Native Americans, according to several GWAS studies (Zhang et al, 2015;Khan et al, 2015b). Our study results showed a negative association with rs2237892 SNP and were in agreement with other global studies (Erfani et al, 2020;Turki et al, 2012). Other studies were found to be positively associated (Yu et al, 2020;Yasuda et al, 2008;Chen et al, 2010).…”

Section: Discussionsupporting

confidence: 92%

Influence of KCNQ1 and TCF7L2 genes associated with the role of type 2 diabetes

Alqadri¹,

Abdelmutalab²,

Abdelhafeez³

et al. 2022

Int. j. adv. appl. sci.

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T2DM is a long-term metabolic disorder characterized by either the pancreas' inability to produce enough insulin or the body's inability to properly utilize the insulin it produces. The β-cell function and blood glucose homeostasis are two areas where TCF7L2 (Transcription factor 7 like 2) appears to be a significant candidate gene. KCNQ1 (potassium voltage-gated channel subfamily, member 1 has been discovered as a T2DM susceptibility gene in Asian populations by genome-wide association studies with rs2237892 polymorphism and an increased risk of developing T2DM. The aim of this study was to investigate the association between rs7903146 and rs2237892 SNP studies in T2DM patients. In this study, 60 T2DM cases and 60 controls were selected. Genotyping was performed for rs7903146 and rs2237892 SNPs using specific primers and restriction enzymes, then all PCR products were loaded on an agarose gel stained with ethidium bromide. The current study results confirmed rs7903146 SNP was strongly associated with genotype (OR-4.14; 95%CI:1.07-15.98; p=0.02) and allele frequencies (OR-4.60; 95%CI:1.66-12.70; p=0.001) whereas in rs2237892 SNP was not associated with any of the genotypes (OR-4.29; 95%CI:0.46-39.58; p=0.16; OR-3.21) or allele frequencies (OR-6.26; 95%CI:0.74-52.83; p=0.055). The current study results were found to be associated with global studies carried out in rs7903146 and rs2237892 SNP. The strength of this current study was to involve Saudi nationalities and we have screened rs7903146 and rs2237892 SNPs which plays a major role in T2DM. Involving 60 T2DM cases/60 controls was the major limitation of this study. Missing validation through Sanger sequencing analysis was one of the limitations of this study. In conclusion, the current study results confirmed rs7903146 SNP was strongly associated with T2DM and rs2237892 SNP was not associated with T2DM patients.

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Section: Discussionsupporting

confidence: 92%

Influence of KCNQ1 and TCF7L2 genes associated with the role of type 2 diabetes

Alqadri¹,

Abdelmutalab²,

Abdelhafeez³

et al. 2022

Int. j. adv. appl. sci.

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“…The family of potassium channels includes (among others) the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) and voltage-gated K+ channel ( KCNQ1 ). The KCNJ11 gene is located 4.5 Kb from ABCC8 on chromosome 11p15.1 and has a single exon encoding for the 390 amino acid Kir6.2 protein, whereas the KCNQ1 gene is located on 11p15.5, encoding the pore-forming a-subunit of the voltage-gated K+ channel (KvLQT1) [ 7 , 8 ]. The expression of potassium channels has been detected in various cells and tissues, including pancreatic islet cells.…”

Section: Introductionmentioning

confidence: 99%

KCNJ11 and KCNQ1 Gene Polymorphisms and Placental Expression in Women with Gestational Diabetes Mellitus

Majcher

Ustianowski

Malinowski

et al. 2022

Genes

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Gestational diabetes mellitus (GDM) represents carbohydrate intolerance in pregnant women. The pathogenesis of GDM is very complex, but abnormalities in insulin production and secretion underlie the disease. Potassium channels play an important role in insulin production and secretion. The family of potassium channels includes (among others) the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) and voltage-gated K+ channel (KCNQ1). The aim of the study was to examine the distribution of the KCNJ11 rs5219 and KCNQ1 rs151290 and rs2237892 gene polymorphisms in women with GDM and pregnant women with normal carbohydrate tolerance, to verify whether these polymorphisms are risk factors for GDM. This study included 204 Caucasian pregnant women with GDM and 207 pregnant women with normal glucose tolerance (NGT) from the West Pomeranian region of Poland. The diagnosis of GDM was based on a 75 g oral glucose tolerance test (OGTT) at 24–28 weeks gestation. There were no statistically significant differences in distribution of the KCNJ11 rs5219 and KCNQ1 rs151290 and rs2237892 gene polymorphisms between women with GDM and pregnant women with normal carbohydrate tolerance. Moreover, there were no statistically significant associations between the studied genotypes and the selected clinical parameters in women with GDM. The results of our study suggest that the KCNJ11 rs5219 and KCNQ1 rs2237892 and rs151290 gene polymorphisms are not significant risk factors associated with the development of GDM in our population. There were also no differences in the expression of KCNJ11 and KCNQ1 genes in the placenta of women with GDM and normal carbohydrate tolerance. However, an association between KCNJ11 gene expression in placenta and APGAR score in newborns was found.

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“…Almost all the genes associated with the lead SNPs of S2 are reported associated with T2DM before, including IGF2BP2 and TCF7L2 . For example, GCKR is a hepatocyte-specific inhibitor of the glucose-metabolizing enzyme glucokinase 26 ; IRS1 plays a critical role in insulin-signalling pathways 27 ; A paralog of ELF5A2 is associated with T2DM 28 ; CDKAL1 are involved in misfolded insulin, leading to oxidative and ER stress in the pancreatic β-cells 29 ; DGKB is causally associated with T2DM 30 ; JAZF1 directly and negatively regulates insulin gene transcription 31 ; a loss-of-function of SLC30A8 protects against T2DM 32 ; HHEX are repeatedly associated with T2DM 33 ; KCNQ1 is highly associate with the risk of T2DM 34 ; ARAP1 is located near risk alleles for T2DM 35 ; a variant of CCND2 could reduce risk of T2DM by half 36 ; HMG20A is a key for the functional maturity of islet β cell 37 . The consistence between our results and these reported associations indicates the reliably of our GWASs results for the two subtypes.…”

Section: Resultsmentioning

confidence: 99%

Identification of distinct trajectories in preclinical type 2 diabetes and their associations with outcomes

Huang

2024

Preprint

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Type 2 Diabetes Mellitus (T2DM) is increasingly prevalent and significantly impacts patients' lives. However, the phenotypic and genetic heterogeneity of the preclinical stage of T2DM, along with the subsequent effects on various clinical outcomes, remain unclear, impeding progress in disease screening and prevention. To address this gap, we employed a robust machine learning algorithm (Subtype and Stage Inference, SuStaIn) with cross-sectional clinical data from the UK Biobank (20,305 preclinical-T2DM participants and 20,305 controls) to identify underlying subtypes and their progression trajectories for preclinical-T2DM. Our analysis revealed one subtype distinguished by elevated circulating leptin levels and decreased leptin receptor levels, coupled with increased BMI, diminished lipid metabolism, and heightened susceptibility to psychiatric conditions such as anxiety disorder, depression disorder, and bipolar disorder. Conversely, individuals in the second subtype manifested typical abnormalities in glucose metabolism, including rising glucose and HbA1c levels, with observed correlations with neurodegenerative disorders. Over ten-year follow-up observations of these individuals reveal differential deterioration in brain and heart organs, and statistically significant difference in disease risk and clinical outcomes between the two subtypes. Our findings indicate a heterogenous pathobiological basis underlying the progression of preclinical-T2DM, with clinical implications for understanding human health from a multiorgan perspective, and improving disease risk screening, prediction, and prevention efforts.

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KCNQ1 common genetic variant and type 2 diabetes mellitus risk

Cited by 8 publications

References 23 publications

Influence of KCNQ1 and TCF7L2 genes associated with the role of type 2 diabetes

Influence of KCNQ1 and TCF7L2 genes associated with the role of type 2 diabetes

KCNJ11 and KCNQ1 Gene Polymorphisms and Placental Expression in Women with Gestational Diabetes Mellitus

Identification of distinct trajectories in preclinical type 2 diabetes and their associations with outcomes

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