HTRA1 methylation in peripheral blood as a potential marker for the preclinical detection of stroke: a case–control study and a prospective nested case–control study

Abstract

Background Stroke is the leading cause of mortality in China. DNA methylation has essential roles in multiple diseases, but its association with stroke was barely studied. We hereby explored the association between blood-based HTRA serine protease 1 (HTRA1) methylation and the risk of stroke. Results The association was discovered in a hospital-based case–control study (cases/controls = 190:190) and further validated in a prospective nested case–control study including 139 cases who developed stroke within 2 years after recruitment and 144 matched stroke-free controls. We observed stroke-related altered HTRA1 methylation and expression in both case–control study and prospective study. This blood-based HTRA1 methylation was associated with stroke independently from the known risk factors and mostly affected the older population. The prospective results further showed that the altered HTRA1 methylation was detectable 2 years before the clinical determination of stroke and became more robust with increased discriminatory power for stroke along with time when combined with other known stroke-related variables [onset time ≤ 1 year: area under the curve (AUC) = 0.76]. Conclusions In our study, altered HTRA1 methylation was associated with stroke at clinical and preclinical stages and thus may provide a potential biomarker in the blood for the risk evaluation and preclinical detection of stroke.

The Spectrum of the Heterozygous Effect in Biallelic Mendelian Diseases—The Symptomatic Heterozygote Issue

“…Here, males have vascular risk factors more frequently than female CARASIL patients. In CARASIL, more than 50 symptomatic carriers have been reported, although most parents were asymptomatic [ 88 ]. For CARASIL, both gender and environmental factors may be involved, as strict risk factor control decreases the risk.…”

Hypomethylation of DYRK4 in peripheral blood is associated with increased lung cancer risk

“…32 Here, we detected the methylation level of DYRK4 in peripheral blood DNA in case-control studies to investigate the association between the methylation of DYRK4 and LC. Finally, the possible association between DYRK4 methylation and LC was validated in a nested case-control study based on the prospective Jurong Study which was described by Liu et al 33 Briefly, subjects recruited in the Jurong cohort were reported to be cancerfree at baseline. Seventeen subjects who developed LC within 2 years after the enrollment were included in the validation as pre-LC cases (average age 69.4 years), and 144 participants who remained cancer and cardiovascular disease-free during the 2.71-year follow-up time were selected as controls (average age 67.6 years).…”

Correction : HTRA1 methylation in peripheral blood as a potential marker for the preclinical detection of stroke: a case–control study and a prospective nested case–control study

“…Following publication of the original article [ 1 ], the authors have realized that ethics statement and Acknowledgement Section are incomplete. The corrected ethics statement should read as follows:…”