冠心病（CHD）和中风已成为全球过早死亡和发病的主要原因。因此，迫切需要敏感、准确的生物标志物来早期检测冠心病和中风，以进行有效的预防和治疗。我们的目的是调查中国人群血液中 HYAL2 甲基化与冠心病和中风风险之间的关联。在一项前瞻性巢式病例对照研究中，纳入了 171 名先心病患者、139 名在招募后出现疾病的中风患者以及 356 名对照者。在 2.5 年的随访期间保持健康，使用质谱法量化外周血中 HYAL2 的甲基化水平，并通过调整协变量的逻辑回归计算关联性。外周血中 HYAL2 甲基化与增加之间存在显着相关性确定了临床前 CHD 和中风的风险 [CHD 中 HYAL2_CpG_1、HYAL2_CpG_2 和 HYAL2_CpG_3 的每 - 10% 甲基化比值比 (OR)：1.35-1.64，p≤ 0.045；每 - 10% 甲基化的 OR：0.76-1.64，对于中风中的 HYAL2_CpG_2 和 HYAL2_CpG_4，p ≤ 0.033]。女性、年龄较小（<70 岁）、无高血压和癌症病史进一步增强了与 CHD 的关联。四个 HYAL2 甲基化位点的组合显示，可以有效地区分无高血压的冠心病和中风病例与对照组 [曲线下面积 (AUC) = 0.78 和 0.75，分别]。这项研究表明，外周血中 HYAL2 甲基化的改变与临床前的临床前症状有很强的相关性。 CHD 和中风，为心血管疾病的风险评估和早期检测提供了一种新型生物标志物。© 2024。作者。

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.© 2024. The Author(s).