Sex-Specific Association of Depression and a Haplotype in Leukotriene A4 Hydrolase Gene

Authors: ZHAO, JINYING - EMORY UNIV SCH OF MED; QUYYUMI, ARSHED - EMORY UNIV SCH OF MED; PATEL, RIYAZ - EMORY UNIV SCH OF MED; QURESHI, IMRANA - EMORY UNIV SCH OF MED; WARREN, FELICIA - EMORY UNIV SCH OF MED; VELEDAR, EMIR - EMORY UNIV SCH OF MED; Onufrak, Stephen; SHALLENBERGER, LUCY - EMORY UNIV SCH OF MED; JONES, LINDA - EMORY UNIV SCH OF MED; GULCHER, JEFFERY - DECODE GENETICS ICELAND; VACCARINO, VIOLA - EMORY UNIV SCH OF MED

Submitted to: Psychosomatic Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/6/2009
Publication Date: 7/21/2009
Citation: Zhao, J., Quyyumi, A.A., Patel, R., Qureshi, I., Warren, F., Veledar, E., Onufrak, S.J., Shallenberger, L.H., Jones, L., Gulcher, J.R., Vaccarino, V. 2009. Sex-Specific Association of Depression and a Haplotype in Leukotriene A4 Hydrolase Gene. Psychosomatic Medicine. Available: http://www.psychosomaticmedicine.org/cgi/content/abstract/PSY.0b013e3181b05c57v1

Interpretive Summary: Risk of clinical depression is, in part, genetically determined and may be related to genes that regulate inflammation. Women are at higher risk of depression than men. The present study compared differences in two genes that regulate inflammation pathways between patients who are clinically depressed and those who are not. The study found that on the LTA4H gene, a specific genetic code named HapE, was associated with lower risk of depression among women but not men. The results provide insight into the possible explanations for differences in depression risk among men and women.

Technical Abstract: Depression is genetically determined and inflammation has been implicated. Women are twice as likely to develop depression as men. Whether genetic variants involved in inflammation play a role in the sex difference in depression is unclear. We examined the association, separately in men and women, between 7 single nucleotide polymorphisms (SNPs) in the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene and 12 SNPs in the leukotriene A4 hydrolase (LTA4H) gene and depression in 1,368 Caucasian subjects (30.4% female) referred for cardiovascular evaluation. Depression was defined as a score = 10 in the Patient Health Questionnaire 9. Single marker analysis was assessed by the '2 test. Haplotype-specific associations were performed using likelihood ratio tests. Empirical significance levels were determined by permutation tests. Depressed individuals, comprising 14.5% of the total, were more likely to be female, current smokers, have a history of diabetes and myocardial infarction. None of the SNPs in the ALOX5AP gene, either singly or in combination, was associated with depression. The 12 SNPs in the LTA4H gene were not individually associated with depression. However, a six-SNP haplotype in LTA4H gene, named HapE, showed a significant protective effect on depression in women, but not in men, after correcting for cardiovascular effects. The interaction between HapE and sex on depression was statistically significant. This study provides the first evidence for a sex-specific association of a novel haplotype in the LTA4H gene on depression. Though replication is needed, our study suggests that genetic variations may underlie sex differences in depression.