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Association between DNA methylation of the KITLG gene and cortisol levels under stress: a replication study

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journal contribution
posted on 2019-04-07, 14:28 authored by Jo Wrigglesworth, Marie-Laure Ancelin, Karen Ritchie, Joanne Ryan

A recent study reported for the first time, that DNA methylation of the KITLG gene mediates the association between childhood trauma and cortisol stress reactivity. Our study aimed to provide the first independent replication of these findings. ESPRIT is a prospective study of community-dwelling participants (age ≥ 65), randomly selected from the electoral rolls of the Montpellier district, in France. Clinical depression was assessed using the Mini-International Neuropsychiatric Interview (MINI, French version 5.00), and the Centre for Epidemiological Studies Depression Scale (CES-D). Experiences of childhood adversity were ascertained via a 25-item questionnaire. Morning, evening, and diurnal salivary cortisol was measured under basal and stress conditions and determined using direct radioimmunoassay analysis. DNA methylation of the KITLG gene was quantified in whole blood using the SEQUENOM MassARRAY EpiTYPER platform. A significant negative association was observed between KITLG DNA methylation and both morning cortisol (β = −1.846 ± 0.666, p = .007) and diurnal cortisol (area under curve [AUC]) (β = −19.429 ± 8.868, p = .031) under a stress condition. However, only the former association was significant after correcting for multiple testing. Further, this association remained after adjusting for age, sex, and depression status. No significant association was observed between childhood trauma and KITLG DNA methylation in this older population. This study provides support for an association between KITLG methylation and stress cortisol levels, suggesting that DNA methylation of this gene may play a role in the longer term regulation of the stress system.Lay summary

  The significant negative association between KITLG DNA methylation and morning cortisol, measured under a stressful condition, suggests that individuals with higher KITLG methylation will secrete lower levels of cortisol whilst under stress.

  The significant negative association between KITLG DNA methylation and morning cortisol, measured under a stressful condition, suggests that individuals with higher KITLG methylation will secrete lower levels of cortisol whilst under stress.

Funding

The ESPRIT project is financed by the regional government of Languedoc-Roussillon, the Agence Nationale de la Recherche Project 07 LVIE 004, and an unconditional grant from Novartis. This work was also supported by France Alzheimer. JR is the recipient of a Dementia Leadership Fellowship from the National Health & Medical Research Council, Australia [APP1135727]. The funders had no role in the design and conduct of the study; in data collection, management, analysis or interpretation of the data and were not involved with the writing, preparation, review or approval of the manuscript. This work was also supported by An unconditional grant from Novartis.

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