title: Sex-specific association of depression and a haplotype in leukotriene A4 hydrolase gene.
abstract: OBJECTIVE
  To assess whether genetic variants involved in inflammation play a role in the sex difference in depression. Depression is, in part, genetically determined and inflammation has been implicated. Women are twice as likely to develop depression as men.
  
  
  METHODS
  We examined the association, separately in men and women, between seven 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 1368 white subjects (30.4% female) referred for cardiovascular evaluation. Depression was defined as a score of >or=10 in the Patient Health Questionnaire 9. Single marker analysis was assessed by the chi(2) test. Haplotype-specific associations were performed, using likelihood ratio tests. Empirical significance levels were determined by permutation tests.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  This study provides the first evidence for a sex-specific association of a novel haplotype in the LTA4H gene on depression. Although replication is needed, our study suggests that genetic variations may underlie sex differences in depression.
authors.affiliation: Department of Biostatistics and Epidemiology, College of Public Health, University of Oklahoma Health Science Center, 801 NE 13th Street, Oklahoma City, OK 73104, USA. Jinying-Zhao@ouhsc.edu
authors.forename: Jinying
authors.initials: J
authors.lastname: Zhao
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
authors.forename: Riyaz
authors.initials: R
authors.lastname: Patel
authors.forename: A Maziar
authors.initials: AM
authors.lastname: Zafari
authors.forename: Emir
authors.initials: E
authors.lastname: Veledar
authors.forename: Stephen
authors.initials: S
authors.lastname: Onufrak
authors.forename: Lucy H
authors.initials: LH
authors.lastname: Shallenberger
authors.forename: Linda
authors.initials: L
authors.lastname: Jones
authors.forename: Viola
authors.initials: V
authors.lastname: Vaccarino
mesh_terms: D058927:5-Lipoxygenase-Activating Proteins; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002874:Chromosome Mapping; D003866:Depressive Disorder / Q000453:epidemiology / Q000235:genetics*; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D023281:Genomics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000453:epidemiology
chemical_list: D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; D008565:Membrane Proteins; D001094:Arachidonate 5-Lipoxygenase; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase