Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
Division of Clinical Epidemiology, Affiliated Geriatric Hospital of Nanjing Medical University, Nanjing, China.
Clin Epigenetics. 2024 Sep 16;16(1):130. doi: 10.1186/s13148-024-01742-7.
Coronary heart disease (CHD) and stroke have become the leading cause of premature mortality and morbidity worldwide. Therefore, sensitive and accurate biomarkers for early detection of CHD and stroke are urgently needed for effective prevention and treatment. We aim to investigate the association between blood-based HYAL2 methylation and the risk of CHD and stroke in Chinese population.
In a prospective nested case-control study comprising 171 CHD cases, 139 stroke cases, who developed the diseases after recruitment and 356 controls who remained healthy during the 2.5 years of follow-up time, the methylation level of HYAL2 in the peripheral blood was quantified using mass spectrometry, and the association was calculated by logistic regression adjusted for covariant.
Significant association between HYAL2 methylation in the peripheral blood and increased risk of preclinical CHD and stroke were identified [odds ratios (ORs) per - 10% methylation: 1.35-1.64, p ≤ 0.045 for HYAL2_CpG_1, HYAL2_CpG_2 and HYAL2_CpG_3 in CHD; ORs per - 10% methylation: 0.76-1.64, p ≤ 0.033 for HYAL2_CpG_2 and HYAL2_CpG_4 in stroke]. The association in CHD was further enhanced by female gender, younger age (< 70 years old), without the history of hypertension and cancer. The combination of four HYAL2 methylation sites showed an effective discrimination of CHD and stroke cases without hypertension from controls [area under curve (AUC) = 0.78 and 0.75, respectively].
This study presents a strong association of altered HYAL2 methylation in peripheral blood with preclinical CHD and stroke, providing a novel biomarker for risk assessment and early detection of cardiovascular diseases.
冠心病（CHD）和中风已成为全球范围内导致过早死亡和发病的主要原因。因此，迫切需要敏感且准确的生物标志物来早期检测 CHD 和中风，以便进行有效的预防和治疗。本研究旨在探讨中国人群血液中 HYAL2 甲基化与 CHD 和中风风险之间的关系。
在一项前瞻性巢式病例对照研究中，纳入了 171 例 CHD 病例、139 例中风病例（招募后发生疾病）和 356 例在 2.5 年随访期间保持健康的对照者，使用质谱法定量检测外周血中 HYAL2 的甲基化水平，并通过逻辑回归计算调整协变量后的关联。
在外周血 HYAL2 甲基化与临床前 CHD 和中风风险增加之间存在显著关联[每减少 10%甲基化的比值比（OR）：HYAL2_CpG_1、HYAL2_CpG_2 和 HYAL2_CpG_3 与 CHD 相关（OR 每减少 10%甲基化：1.35-1.64，p≤0.045）；HYAL2_CpG_2 和 HYAL2_CpG_4 与中风相关（OR 每减少 10%甲基化：0.76-1.64，p≤0.033）]。在女性、年龄较小（<70 岁）、无高血压和癌症病史的 CHD 患者中，这种关联更为显著。四个 HYAL2 甲基化位点的组合能够有效区分无高血压的 CHD 和中风病例与对照组[曲线下面积（AUC）分别为 0.78 和 0.75]。
本研究表明，外周血中 HYAL2 甲基化的改变与临床前 CHD 和中风之间存在强烈关联，为心血管疾病的风险评估和早期检测提供了一种新的生物标志物。
