Correlation between fasting plasma glucose, HbA1c and DNA methylation in adult twins / 北京大学学报(医学版)

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.

Correlation between blood pressure and DNA methylation in adult twins / 北京大学学报(医学版)

OBJECTIVE@#To explore the DNA methylation sites correlated with blood pressure (systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse pressure) in adult twin population.@*METHODS@#A total of 476 twins from the Chinese National Twin Registry were selected as the research population. Questionnaires were used to collect demographic characteristics, lifestyle, disease status and other information, and blood pressure, height, weight and other anthropometric indicators were measured. The genome-wide DNA methylation of whole blood samples was detected by using Infinium HumanMethylation450 BeadChip. The DNA methylation sites correlated with blood pressure were analyzed by constructing mixed effect model with adjusting potential confounding factors, and the significant level was false discovery rate <0.05.@*RESULTS@#After data quality control, 465 twins (122 pairs of monozygotic twins, 104 pairs of dizygotic twins, 13 individuals from 13 pairs of twins) aged (44.8±13.2) years were finally enrolled. There were more males and more monozygotic twins, and the current smokers and current regular drinkers both accounted for more than 30%. No significant CpG site was found after multiple testing in the correlation study between genome-wide DNA methylation and blood pressure by using the collected twins. However, the cg07761116 located on chromosome 10 had low P value in the correlation analysis of 3 blood pressure indices (systolic blood pressure, diastolic blood pressure, mean arterial pressure), suggesting that this site might be correlated with blood pressure. The other 7 sites had low P value in the correlation analysis of the two blood pressure indices, respectively, which pointed to genes involved in neurological development, protein homeostasis, inflammatory reaction and other pathways.@*CONCLUSION@#There is no sufficient evidence to support any DNA methylation site correlated with blood pressure, which may be caused by insufficient sample size and other reasons. This study could provide a reference for subsequent similar twin studies, and subsequent studies can focus on the cg07761116 located on chromosome 10 and other sites with low P values.