Chia-Ni Hsiung 1,2 , Yi-Cheng Chang 2,3 , Chien-Wei Lin 4 , Chia-Wei Chang 4 , Wen-Cheng Chou 2 , Hou-Wei Chu 4 , Ming-Wei Su 4 , Pei-Ei Wu 4 , Chen-Yang Shen 2,5 Show Affiliations »
Abstract
CONTEXT: The association between circulating triglyceride (TG) and glycated hemoglobin A1c (HbA1c), a biomarker for type 2 diabetes, has been widely addressed, but the causal direction of the relationship is still ambiguous. OBJECTIVE: To confirm the causal relationship between TG and HbA1c by using bidirectional and 2-step Mendelian randomization (MR) approaches. METHODS: We carried out a bidirectional MR approach using the summarized results from the public database to examine any potential causal effects between serum TG and HbA1c in 16 000 individuals of the Taiwan Biobank cohort. We used the MR estimate and the MR inverse variance-weighted method to reveal that relationship between TG and HbA1c. To further determine whether the DNA methylation at specific sequences mediate the causal pathway between TG and HbA1c, using the 2-step MR approach. RESULTS: We identified that a single-unit increase in TG measured via log transformation of mg/dL data was associated with a significant increase of 10 units of HbA1c (95% CI = 1.05-18.95, P = 0.029). In contrast, the genetic determinants of HbA1c do not contribute to the amount of circulating TG (beta = 1.75, 95% CI = -11.50 to 14.90). Sensitivity analyses, included the weighted-median approach and MR-Egger regression, were performed to confirm no pleiotropic effect among these instrumental variables. Furthermore, we identified the genetic variant, rs1823200, is associated with both methylation of the CpG site adjacent to CADPS gene and HbA1c level. CONCLUSION: Our study suggests that higher circulating TG can have an affect on genomic methylation status, ultimately causing elevated level of circulating HbA1c. © Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
CONTEXT: The association between circulating triglyceride (TG ) and glycated hemoglobin A1c (HbA1c), a biomarker for type 2 diabetes , has been widely addressed, but the causal direction of the relationship is still ambiguous. OBJECTIVE: To confirm the causal relationship between TG and HbA1c by using bidirectional and 2-step Mendelian randomization (MR) approaches. METHODS: We carried out a bidirectional MR approach using the summarized results from the public database to examine any potential causal effects between serum TG and HbA1c in 16 000 individuals of the Taiwan Biobank cohort. We used the MR estimate and the MR inverse variance-weighted method to reveal that relationship between TG and HbA1c. To further determine whether the DNA methylation at specific sequences mediate the causal pathway between TG and HbA1c, using the 2-step MR approach. RESULTS: We identified that a single-unit increase in TG measured via log transformation of mg/dL data was associated with a significant increase of 10 units of HbA1c (95% CI = 1.05-18.95, P = 0.029). In contrast, the genetic determinants of HbA1c do not contribute to the amount of circulating TG (beta = 1.75, 95% CI = -11.50 to 14.90). Sensitivity analyses, included the weighted-median approach and MR-Egger regression, were performed to confirm no pleiotropic effect among these instrumental variables. Furthermore, we identified the genetic variant, rs1823200 , is associated with both methylation of the CpG site adjacent to CADPS gene and HbA1c level. CONCLUSION: Our study suggests that higher circulating TG can have an affect on genomic methylation status, ultimately causing elevated level of circulating HbA1c. © Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Entities: Chemical
Disease
Gene
Mutation
Keywords:
HbA1c; Mendelian randomization; diabetes; phenome-wide association study; triglyceride
Mesh： See more »
Substances： See more »
Year: 2020
PMID： 31784746 DOI： 10.1210/clinem/dgz243
Source DB: PubMed Journal: J Clin Endocrinol Metab ISSN： 0021-972X Impact factor: 5.958