Dayeh Tasnim, Tuomi Tiinamaija, Almgren Peter, Perfilyev Alexander, Jansson Per-Anders, de Mello Vanessa D, Pihlajamäki Jussi, Vaag Allan, Groop Leif, Nilsson Emma, Ling Charlotte
a Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Center , Malmö , Sweden.
b Endocrinology, Abdominal Center, Helsinki University Hospital , Helsinki , Finland.
Epigenetics. 2016 Jul 2;11(7):482-8. doi: 10.1080/15592294.2016.1178418. Epub 2016 May 5.
Identification of subjects with a high risk of developing type 2 diabetes (T2D) is fundamental for prevention of the disease. Consequently, it is essential to search for new biomarkers that can improve the prediction of T2D. The aim of this study was to examine whether 5 DNA methylation loci in blood DNA (ABCG1, PHOSPHO1, SOCS3, SREBF1, and TXNIP), recently reported to be associated with T2D, might predict future T2D in subjects from the Botnia prospective study. We also tested if these CpG sites exhibit altered DNA methylation in human pancreatic islets, liver, adipose tissue, and skeletal muscle from diabetic vs. non-diabetic subjects. DNA methylation at the ABCG1 locus cg06500161 in blood DNA was associated with an increased risk for future T2D (OR = 1.09, 95% CI = 1.02-1.16, P-value = 0.007, Q-value = 0.018), while DNA methylation at the PHOSPHO1 locus cg02650017 in blood DNA was associated with a decreased risk for future T2D (OR = 0.85, 95% CI = 0.75-0.95, P-value = 0.006, Q-value = 0.018) after adjustment for age, gender, fasting glucose, and family relation. Furthermore, the level of DNA methylation at the ABCG1 locus cg06500161 in blood DNA correlated positively with BMI, HbA1c, fasting insulin, and triglyceride levels, and was increased in adipose tissue and blood from the diabetic twin among monozygotic twin pairs discordant for T2D. DNA methylation at the PHOSPHO1 locus cg02650017 in blood correlated positively with HDL levels, and was decreased in skeletal muscle from diabetic vs. non-diabetic monozygotic twins. DNA methylation of cg18181703 (SOCS3), cg11024682 (SREBF1), and cg19693031 (TXNIP) was not associated with future T2D risk in subjects from the Botnia prospective study.
识别具有发生2型糖尿病（T2D）高风险的个体对于预防该疾病至关重要。因此，寻找能够改善T2D预测的新生物标志物至关重要。本研究的目的是检验血液DNA中的5个DNA甲基化位点（ABCG1、PHOSPHO1、SOCS3、SREBF1和TXNIP），最近报道它们与T2D相关，是否可以预测来自博特尼亚前瞻性研究的个体未来发生T2D的情况。我们还测试了这些CpG位点在糖尿病患者与非糖尿病患者的人胰岛、肝脏、脂肪组织和骨骼肌中是否表现出DNA甲基化改变。血液DNA中ABCG1位点cg06500161处的DNA甲基化与未来发生T2D的风险增加相关（OR = 1.09，95% CI = 1.02 - 1.16，P值 = 0.007，Q值 = 0.018），而血液DNA中PHOSPHO1位点cg0265（此处原文有误，应为cg02650017）处的DNA甲基化与未来发生T2D的风险降低相关（OR = 0.85，95% CI = 0.75 - 0.95，P值 = 0.006，Q值 = 0.018），在调整年龄、性别、空腹血糖和家族关系后。此外，血液DNA中ABCG1位点cg06500161处的DNA甲基化水平与BMI、糖化血红蛋白、空腹胰岛素和甘油三酯水平呈正相关，并且在T2D不一致的同卵双胞胎对中，糖尿病双胞胎的脂肪组织和血液中的该水平升高。血液中PHOSPHO1位点cg02650017处的DNA甲基化与高密度脂蛋白水平呈正相关，并且在糖尿病与非糖尿病同卵双胞胎的骨骼肌中降低。博特尼亚前瞻性研究中个体的cg18181703（SOCS3）、cg11024682（SREBF1）和cg19693031（TXNIP）的DNA甲基化与未来T2D风险无关。
