DNA methylation of loci within ABCG1 and PHOSPHO1 in blood DNA is associated with future type 2 diabetes risk.
DNA methylation of loci within ABCG1 and PHOSPHO1 in blood DNA is associated with future type 2 diabetes risk.
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DOI：
10.1080/15592294.2016.1178418
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发表时间：
2016-07-02
期刊：
影响因子：
3.7
通讯作者：
Ling C
中科院分区：
文献类型：
--
作者：
Dayeh T;Tuomi T;Almgren P;Perfilyev A;Jansson PA;de Mello VD;Pihlajamäki J;Vaag A;Groop L;Nilsson E;Ling C
2型糖尿病（T2D）高危人群的识别是预防该疾病的基础。因此，有必要寻找新的生物标志物，可以提高T2D的预测。本研究的目的是研究最近报道的与T2D相关的血液DNA中的5个DNA甲基化位点（ABCG1、PHOSPHO1、SOCS3、SREBF1和TXNIP）是否可以预测博特尼亚前瞻性研究中受试者的未来T2D。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胰岛、肝脏、脂肪组织和骨骼肌中是否表现出DNA甲基化的改变。在调整年龄、性别、空腹血糖和家庭关系后，血液DNA中ABCG1位点cg06500161的DNA甲基化与未来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cg02650017的DNA甲基化与未来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）。此外，血液DNA中ABCG1位点cg06500161的DNA甲基化水平与BMI、HbA1c、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中，糖尿病双胞胎的脂肪组织和血液中甲基化水平升高。血液中PHOSPHO1位点cg02650017的DNA甲基化与HDL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甲基化降低。在博特尼亚前瞻性研究的受试者中，cg18181703 （SOCS3）、cg11024682 （SREBF1）和cg19693031 （TXNIP）的DNA甲基化与未来的T2D风险无关。
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.