Connors-BRI Symposium

Incorporating Sex as Biologic Variable to Advance Health

May 24, 2021 | 3-5PM

Virtual Event

Wasita Parksook, MD, MSc

Brigham and Women’s Hospital
Endocrinology, Diabetes & Hypertension


LSD1 risk allele carriers in humans and LSD1 deficiency (LSD1+/-) in mice are linked to salt sensitivity of blood pressure (SSBP). LSD1 risk allele carriers have greater SSBP than non-risk allele individuals in hypertensive African descent (AD). LSD1+/- mice display increased aldosterone production or mineralocorticoid receptor (MR) expression. However, only LSD1+/- male mice show greater SSBP. We hypothesized that LSD1 gene variants in humans leads to aldosterone dysregulation resulting in SSBP, in which the response could be race-, sex-, and -age specific. To test this hypothesis, we analyzed data from the HyperPATH cohort in 297 normotensives and hypertensives of AD and European descent (ED). Multiple regression analyses with adjustments were performed for outcome variables. In the AD, but not the ED, LSD1 risk allele carriers had greater SSBP than non-risk allele individuals. In the AD, female LSD1 risk allele carriers had greater SSBP, in which SSBP was significant mainly in women of low estrogen state. There was a significant LSD1 genotype-sex interaction in aldosterone response to angiotensin II stimulation in individuals age ≤50 years. Female LSD1 risk allele carriers had lower aldosterone response to angiotensin II stimulation. This response was driven by women of replete estrogen state. The mechanisms related to the resistance to develop SSBP in females is uncertain but may be related to estrogen modulating the effect of MR activation as seen in LSD1+/- female mice. Collectively, these data suggest that LSD1 female risk allele carriers of ADs, especially if post-menopausal, may be candidates for MR antagonists.


3PM – Welcome Remarks
3:05PM – Keynote Address
3:45PM – Featured Short Talks
4:20PM – Lightning Talks
4:50PM – Closing Remarks

Keynote Speaker

Janine Austin Clayton, MD

Janine Austin Clayton, M.D., Associate Director for Research on Women’s Health and Director of the Office of Research on Women’s Health (ORWH) at the National Institutes of Health (NIH), is the architect of the NIH policy requiring scientists to consider sex as a biological variable across the research spectrum. This policy is part of NIH’s initiative to enhance reproducibility through rigor and transparency. As co-chair of the NIH Working Group on Women in Biomedical Careers with NIH Director Dr. Francis Collins, Dr. Clayton also leads NIH’s efforts to advance women in science careers.

Prior to joining the ORWH, Dr. Clayton was the Deputy Clinical Director of the National Eye Institute (NEI) for seven years. A board-certified ophthalmologist, Dr. Clayton’s research interests include autoimmune ocular diseases and the role of sex and gender in health and disease. She is the author of more than 120 scientific publications, journal articles, and book chapters.
Dr. Clayton, a native Washingtonian, received her undergraduate degree with honors from Johns Hopkins University and her medical degree from Howard University College of Medicine. She completed a residency in ophthalmology at the Medical College of Virginia. Dr. Clayton completed fellowship training in cornea and external disease at the Wilmer Eye Institute at Johns Hopkins Hospital and in uveitis and ocular immunology at NEI.

Dr. Clayton has received numerous awards, including the Senior Achievement Award from the Board of Trustees of the American Academy of Ophthalmology in 2008 and the European Uveitis Patient Interest Association Clinical Uveitis Research Award in 2010. She was selected as a 2010 Silver Fellow by the Association for Research in Vision and Ophthalmology. In 2015, she was awarded the American Medical Women’s Association Lila A. Wallis Women’s Health Award and the Wenger Award for Excellence in Public Service. Dr. Clayton was granted the Bernadine Healy Award for Visionary Leadership in Women’s Health in 2016. She was also selected as an honoree for the Woman’s Day Red Dress Awards and the American Medical Association’s Dr. Nathan Davis Awards for Outstanding Government Service in 2017.