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Folate, or vitamin B9, is essential for a healthy pregnancy, and folic acid supplements are known to prevent birth defects of the brain and spine. Less is known about the receptors that help use folate. One of them, folate receptor beta, is made almost exclusively by macrophages, immune cells that fight infection and regulate inflammation, and is especially abundant in the placenta.
Digna Velez Edwards, PhD, of the Department of Obstetrics and Gynecology at Vanderbilt Heath, and colleagues, in collaboration with David Aronoff, MD, of Indiana University School of Medicine, asked whether rare changes in the gene for this receptor, called FOLR2, are tied to human health conditions. They analyzed de-identified electronic health records and genetic data from 170,889 people of African and European ancestry in Vanderbilt’s BioVU biobank and the national eMERGE Network, testing more than 1,200 conditions.
Rare variants that alter the receptor protein were linked to developmental disorders, mainly attention-deficit/hyperactivity disorder (ADHD), and to genital and urinary tract infections during pregnancy. Other rare variants, including some that may affect how the gene is regulated, were linked to tension headaches and to pregnancy complications such as high blood pressure and problems with the membranes surrounding the fetus. Eye inflammation and painful intercourse also showed suggestive links in people of African ancestry.
The findings, reported in the journal Frontiers in Immunology, show association, not cause, and need to be confirmed in larger, more diverse groups. Still, they suggest that macrophages and folate receptors may influence brain development and pregnancy health, and they point to a gene worth studying further.
Other authors include Elizabeth Jasper, PhD; James Jaworski, MD; Yuan Luo; Bahram Namjou Khales; and Atlas Khan. Velez Edwards holds the Lucius E. Burch Chair of Reproductive Physiology and Family Planning. The study reported no dedicated funding. Jasper was supported by the National Institutes of Health (grant K12HD043483).
