News Release: Research, School of Medicine

Aug. 5,  2009

Gene Variant Protects from Depression in Women Only

News Article ImageViola Vaccarino, MD, PhD, senior author of the study

A variant of an inflammation-related gene protects women but not men from depression, according to researchers at Emory University School of Medicine.

The finding comes from studying 1,368 people being examined for possible heart disease at Emory since 2004. The results were published online in July ahead of print in the journal Psychosomatic Medicine.

Having the variant, called HapE, made a woman less likely to be depressed. The prevalence of HapE was 6.4 percent among depressed women and 19.7 percent among nondepressed women. The corresponding frequencies were 13.7 percent and 13.9 percent in men.

The lead author is Jinying Zhao, MD, PhD, now associate professor of biostatistics and epidemiology at the University of Oklahoma Health Science Center. The senior author was Viola Vaccarino, MD, PhD, professor of medicine (cardiology) at Emory University School of Medicine.

"Although replication is needed, our study suggests that genetic variations may underlie sex differences in depression," the authors write. "This result may explain why both depression and cardiovascular disease have been linked to an increased inflammatory response."

This individual gene variant appears to be the first to show a difference between men and women in depression susceptibility, Zhao says.

Inflammation plays a role in driving depression, and anti-inflammatory medications are being tested as possible treatments for depression. The finding suggests that men and women might respond differently to such treatments depending on their genetic background.

Women are about twice as likely to experience depression compared with men, and previous studies have shown that the heritability of major depression is higher in women than in men.

The variant HapE is a "haplotype," or a group of alternative spellings of a gene often found together, in the gene encoding leukotriene A4 hydrolase (LTA4H). How the haplotype changes the regulation of the gene is not yet known.

Leukotrienes have been extensively studied for their ability to attract white blood cells and constrict the airways in asthma. LTA4H is an enzyme that has been linked to risk for developing both asthma and heart disease.

The leukotriene pathway is "a likely candidate in the search for a common genetic mechanism linking depression and cardiovascular disease," the authors write.

Because the group studied at Emory was being examined for heart disease, had an average age of 62.7 and was mostly Caucasian, the authors say that the gene variant needs to be tested in other population groups - for example, non-Caucasians, people who are younger or who don't have heart disease.

The research was supported by the American Heart Association and the National Institutes of Health.


J. Zhao et al. Sex-specific association of depression and a haplotype in leukotriene A4 hydrolase gene Psychosom. Med. 71, x-y (2009).

Helgadottir et al. A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction. Nat Genet 38, 68-74 (2006)


The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service. Its components include schools of medicine, nursing, and public health; Yerkes National Primate Research Center; the Emory Winship Cancer Institute; and Emory Healthcare, the largest, most comprehensive health system in Georgia. The Woodruff Health Sciences Center has a $2.3 billion budget, 17,000 employees, 2,300 full-time and 1,900 affiliated faculty, 4,300 students and trainees, and a $4.9 billion economic impact on metro Atlanta.

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