Correlation between fasting plasma glucose, HbA1c and DNA methylation in adult twins.
10.19723/j.issn.1671-167X.2020.03.005
- Author:
Zhao Nian WANG
1
;
Wen Jing GAO
1
;
Bi Qi WANG
1
;
Wei Hua CAO
1
;
Jun LV
1
;
Can Qing YU
1
;
Zeng Chang PANG
2
;
Li Ming CONG
3
;
Hua WANG
4
;
Xian Ping WU
5
;
Yu LIU
6
;
Li Ming LI
1
Author Information
1. Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing 100191, China.
2. Qingdao Municipal Center for Disease Control and Prevention, Qingdao 266033, Shandong, China.
3. Zhejiang Center for Disease Control and Prevention, Hangzhou 310051, China.
4. Jiangsu Center for Disease Control and Prevention, Nanjing 210009, China.
5. Sichuan Center for Disease Control and Prevention, Chengdu 610041, China.
6. Center for Disease Control and prevention, Heilongjiang Agricultural Reclamation Bureau, Harbin 150090, China.
- Publication Type:Twin Study
- Keywords:
DNA methylation;
Fasting plasma glucose;
Glycated haemoglobin;
Twin
- MeSH:
Adult;
Blood Glucose;
CpG Islands;
DNA Methylation;
Epigenesis, Genetic;
Fasting;
Female;
Glycated Hemoglobin A;
Humans;
Male;
Middle Aged;
Twins, Monozygotic
- From:
Journal of Peking University(Health Sciences)
2020;52(3):425-431
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the cytidine-phosphate-guanosine (CPG) sites associated with fas-ting plasma glucose (FPG) and glycated haemoglobin (HbA1c) in twins.
METHODS:In the study, 169 pairs of monozygotic twins were recruited in Qingdao, Zhejiang, Jiangsu, Sichuan and Heilongjiang in June to December of 2013 and June 2017 to October 2018. The methylation was detected by Illumina Infinium HumanMethylation450 BeadChip and Illumina Infinium MethylationEPIC BeadChip. According to the Linear Mixed Effect model (LME model), fasting plasma glucose and HbA1c were taken as the main effects, the methylation level (β value) was taken as the dependent variable, continuous variables, such as age, body mass index (BMI), blood pressure, components of blood cells, surrogate variables generated by SVA, and categorical variables, such as gender, smoking and drinking status, hypoglycemic drugs taking, were included in the fixed effect model as covariates, and the identity numbers (ID) of the twins was included in the random effect model. The intercept was set as a random. Regression analysis was carried out to find out the CpG sites related to fasting blood glucose or HbA1c, respectively.
RESULTS:In this study, 338 monozygotic twins (169 pairs) were included, with 412 459 CpG loci. Among them, 114 pairs were male, and 55 pairs were female, with an average age of (48.2±11.9) years. After adjustment of age, gender, BMI, blood pressure, smoking, drinking, blood cell composition, and other covariates, and multiple comparison test, 7 CpG sites (cg19693031, cg01538969, cg08501915, cg04816311, ch.8.1820050F, cg06721411, cg26608667) were found related to fasting blood glucose, 3 of which (cg08501915, ch.8.1820050f, cg26608667) were the newly found sites in this study; whereas 10 CpG sites (cg19693031, cg04816311, cg01538969, cg01339781, cg01676795, cg24667115, cg09029192, cg20697417, ch.4.1528651F, cg16097041) were found related to HbA1c, and 4 of which(cg01339781, cg24667115, cg20697417, and ch.4.1528651f) were new. We found that cg19693031 in TXNIP gene was the lowest P-value site in the association analysis between DNA methylation and fas-ting plasma glucose and HbA1c (PFPG=2.42×10-19, FDRFPG<0.001; PHbA1c=1.72×10-19, FDRHbA1c<0.001).
CONCLUSION:In this twin study, we found new CpG sites related to fasting blood glucose and HbA1c, and provided some clues that partly revealed the potential mechanism of blood glucose metabolism in terms of DNA methylation, but it needed further verification in external larger samples.
