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CN 34-1304/RISSN 1674-3679

Volume 25 Issue 6
Jul.  2021
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WANG Ting-ting, SU Ping, SUN Xiao-ru, YU Yuan-yuan, LI Hong-kai, XUE Fu-zhong. DNA methylation mediates the effect of BMI on insulin-treated gestational diabetes mellitus[J]. CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION, 2021, 25(6): 650-655. doi: 10.16462/j.cnki.zhjbkz.2021.06.006
Citation: WANG Ting-ting, SU Ping, SUN Xiao-ru, YU Yuan-yuan, LI Hong-kai, XUE Fu-zhong. DNA methylation mediates the effect of BMI on insulin-treated gestational diabetes mellitus[J]. CHINESE JOURNAL OF DISEASE CONTROL & PREVENTION, 2021, 25(6): 650-655. doi: 10.16462/j.cnki.zhjbkz.2021.06.006

DNA methylation mediates the effect of BMI on insulin-treated gestational diabetes mellitus

doi: 10.16462/j.cnki.zhjbkz.2021.06.006
Funds:

National Key Research and Development Program 2020YFC2003500

National Natural Science Foundation of China 81773547

National Natural Science Foundation of China 82003557

National Natural Science Foundation of Shandong Province ZR2019ZD02

National Natural Science Foundation of Shandong Province ZR2019PH041

More Information
  •   Objective  To explore the mediate role of DNA methylation between body mass index (BMI) and insulin-treated gestational diabetes mellitus (I-GDM) and further estimate its mediation effect.  Methods  Based on Gene Expression Omnibus (GEO) data repository (accession number GSE88929), obstetricians collected 44 I-GDM and 64 controls, which included a total of 212 991 cytosine-phosphate-guanine pairs of nucleotides (CpG) sites. A causal inference test (CIT) was used to select potential mediator of CpG sites. Furthermore, after adjusting for confounding factors including maternal age, fetal sex, and gestational age, we estimated the mediation effect of BMI on I-GDM by CpG sites.  Results  In CIT process, step 1 results showed that BMI was associated with I-GDM (OR=1.057, 95% CI: 1.014-1.105, P=0.010). Step 2 results indicated that 6 348 CpG after adopting FDR correction were associated with I-GDM conditional on BMI. Step 3 results manifested that 529 CpG were associated with BMI adjusting for I-GDM. Step 4 results showed that I-GDM was independent of BMI after adjusting 6 CpG. Therefore, CIT detected 6 CpG sites (cg00542041, cg08589721, cg25775742, cg15819225, cg26824326, cg15110463) as mediators between BMI and I-GDM. The above 6 CpG showed significant mediation effects by a causal inference model of mediation analysis.  Conclusion  Our research identified 6 DNA methylation CpG sites, which represent a potential mediation relationship between BMI and I-GDM. These findings suggest that the 6 CpG may serve as novel biomarkers and provide an essential reference for studying the complex biological mechanism between BMI and I-GDM.
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