Dataset Information

Pleiotropic Effects of a KCNQ1 Variant on Lipid Profiles and Type 2 Diabetes: A Family-Based Study in China.

ABSTRACT:

Objective

The genetic variant rs2237895, located in the Potassium Voltage-Gated Channel Subfamily Q Member 1 (KCNQ1) gene, has been replicated to be associated with type 2 diabetes mellitus (T2DM) susceptibility, but the relationship with lipids is conflicting. Furthermore, the common genetic predisposition to T2DM and lipids was not fully detected.

Methods

In total, 5839 individuals (2220 were T2DM patients) across 2885 families were included. The effect of rs2237895 on T2DM and lipids was estimated using linear regression and logistic regression models after adjustment for multiple covariates. Mediation analysis was then used to test whether KCNQ1 participated in T2DM pathogenesis via lipid-mediated pathways.

Results

Per allele-C of rs2237895 was associated with 17% (11-23%, P < 0.001) increased T2DM risk. Moreover, it was correlated with 5% (1-9%, P < 0.001) increased T2DM risk. Moreover, it was correlated with 5% (1-9%, P < 0.001) increased T2DM risk. Moreover, it was correlated with 5% (1-9%, P < 0.001) increased T2DM risk. Moreover, it was correlated with 5% (1-9%, P < 0.001) increased T2DM risk. Moreover, it was correlated with 5% (1-9%, P < 0.001) increased T2DM risk. Moreover, it was correlated with 5% (1-9%.

Conclusion

KCNQ1 had pleiotropic effects on lipids and T2DM, and the unexpected genetic effect on association of HDL-C with T2DM was observed, indicating the different pathways to lipids and T2DM. Further research studies are needed to verify potential biological mechanisms.

SUBMITTER: Wang X

PROVIDER: S-EPMC6982365 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Pleiotropic Effects of a KCNQ1 Variant on Lipid Profiles and Type 2 Diabetes: A Family-Based Study in China.

Wang Xiaowen X Wu Junhui J Wu Yao Y Wang Mengying M Wang Zijing Z Wu Tao T Chen Dafang D Tang Xun X Qin Xueying X Wu Yiqun Y Hu Yonghua Y

Journal of diabetes research 20200113

<h4>Objective</h4>The genetic variant rs2237895, located in the Potassium Voltage-Gated Channel Subfamily Q Member 1 (KCNQ1) gene, has been replicated to be associated with type 2 diabetes mellitus (T2DM) susceptibility, but the relationship with lipids is conflicting. Furthermore, the common genetic predisposition to T2DM and lipids was not fully detected.<h4>Methods</h4>In total, 5839 individuals (2220 were T2DM patients) across 2885 families were included. The effect of rs2237895 on T2DM and ...[more]

PMID: 32016123

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Project description:Background: Accumulated evidence suggests that adverse lipid changes are risk factors for type 2 diabetes mellitus (T2DM) and neurodegenerative disorders. The ATP-binding cassette A1 transporter (ABCA1) gene contributes to both lipid processing and amyloid-β formation and thus shows promise as a biological target in the pathology of mild cognitive impairment (MCI) in T2DM. Objective: This study aimed to investigate the interactions among lipids, ABCA1 R219K polymorphism, and cognitive function in T2DM. Methods: Clinical parameters, including lipids, were measured. The testing scores of different cognitive domains were recorded, and the ABCA1 R219K polymorphisms were analyzed. Results: A total of 226 patients, including 124 MCI patients and 102 controls, were enrolled in this study. T2DM patients with MCI showed lower cognitive functions, serum high-density lipoprotein (HDL-c), and apolipoprotein A1 (apoA-I) levels; and higher total cholesterol level than the controls. Serum HDL-c (P = 0.001) and apoA-I (P = 0.016) were positively associated with the MoCA score in MCI patients. Further stratification analyses revealed that the subjects with higher HDL-c concentration showed better attention and memory for verbal, visual, and logical functions than the group with lower HDL-c concentration (P < 0.05). No significant differences were observed among the distributions of ABCA1 R219K variants between MCI patients and controls; however, the KK genotype carriers presented higher apoA-I levels than those with RR genotype in MCI individuals. Conclusion: This study does not support the association between R219K polymorphism and T2DM-related MCI. However, our data suggested that the serum HDL-c level might positively influence cognition, especially memory function, in T2DM patients. Further studies are needed to determine the interaction between lipids and ABCA1 genotype and its effect on cognition in T2DM patients. Trial registration: Advanced Glycation End Products Induced Cognitive Impairment in Diabetes: BDNF Signal Meditated Hippocampal Neurogenesis ChiCTR-OCC-15006060; http://www.chictr.org.cn/showproj.aspx?proj=10536.

Dataset Information

Pleiotropic Effects of a KCNQ1 Variant on Lipid Profiles and Type 2 Diabetes: A Family-Based Study in China.

Objective

Methods

Results

Conclusion

Publications

Pleiotropic Effects of a KCNQ1 Variant on Lipid Profiles and Type 2 Diabetes: A Family-Based Study in China.

Similar Datasets

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