Pleiotropic Effects of a KCNQ1 Variant on Lipid Profiles and Type 2 Diabetes: A Family-Based Study in China
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 predi...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2020/8278574 |
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| author | Xiaowen Wang Junhui Wu Yao Wu Mengying Wang Zijing Wang Tao Wu Dafang Chen Xun Tang Xueying Qin Yiqun Wu Yonghua Hu |
| author_facet | Xiaowen Wang Junhui Wu Yao Wu Mengying Wang Zijing Wang Tao Wu Dafang Chen Xun Tang Xueying Qin Yiqun Wu Yonghua Hu |
| author_sort | Xiaowen Wang |
| collection | DOAJ |
| description | 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=0.019), 4% (1-7%, P=0.019), 2% (0-3%, P=0.045), and 2% (0-3%, P=0.009) higher total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A, and apolipoprotein B (Apo-B) concentrations, respectively. Nevertheless, the genetic susceptibility for higher T2DM risk was correlated with higher high-density lipoprotein cholesterol (HDL-C) level (2%, 0-3%, P=0.026). Mediation analysis showed only TC, LDL-C, and Apo-B had small significant mediated effects, with 2.9%, 2.3%, and 3.1% of the total effects of rs2237895 on T2DM being mediated by them, respectively. 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. |
| format | Article |
| id | doaj-art-a28aae3ae9d94e4d92374d709307f1bb |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-a28aae3ae9d94e4d92374d709307f1bb2025-02-03T01:24:39ZengWileyJournal of Diabetes Research2314-67452314-67532020-01-01202010.1155/2020/82785748278574Pleiotropic Effects of a KCNQ1 Variant on Lipid Profiles and Type 2 Diabetes: A Family-Based Study in ChinaXiaowen Wang0Junhui Wu1Yao Wu2Mengying Wang3Zijing Wang4Tao Wu5Dafang Chen6Xun Tang7Xueying Qin8Yiqun Wu9Yonghua Hu10Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, ChinaObjective. 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=0.019), 4% (1-7%, P=0.019), 2% (0-3%, P=0.045), and 2% (0-3%, P=0.009) higher total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A, and apolipoprotein B (Apo-B) concentrations, respectively. Nevertheless, the genetic susceptibility for higher T2DM risk was correlated with higher high-density lipoprotein cholesterol (HDL-C) level (2%, 0-3%, P=0.026). Mediation analysis showed only TC, LDL-C, and Apo-B had small significant mediated effects, with 2.9%, 2.3%, and 3.1% of the total effects of rs2237895 on T2DM being mediated by them, respectively. 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.http://dx.doi.org/10.1155/2020/8278574 |
| spellingShingle | Xiaowen Wang Junhui Wu Yao Wu Mengying Wang Zijing Wang Tao Wu Dafang Chen Xun Tang Xueying Qin Yiqun Wu Yonghua Hu Pleiotropic Effects of a KCNQ1 Variant on Lipid Profiles and Type 2 Diabetes: A Family-Based Study in China Journal of Diabetes Research |
| title | Pleiotropic Effects of a KCNQ1 Variant on Lipid Profiles and Type 2 Diabetes: A Family-Based Study in China |
| title_full | Pleiotropic Effects of a KCNQ1 Variant on Lipid Profiles and Type 2 Diabetes: A Family-Based Study in China |
| title_fullStr | Pleiotropic Effects of a KCNQ1 Variant on Lipid Profiles and Type 2 Diabetes: A Family-Based Study in China |
| title_full_unstemmed | Pleiotropic Effects of a KCNQ1 Variant on Lipid Profiles and Type 2 Diabetes: A Family-Based Study in China |
| title_short | Pleiotropic Effects of a KCNQ1 Variant on Lipid Profiles and Type 2 Diabetes: A Family-Based Study in China |
| title_sort | pleiotropic effects of a kcnq1 variant on lipid profiles and type 2 diabetes a family based study in china |
| url | http://dx.doi.org/10.1155/2020/8278574 |
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