title: Association between a common CYP17A1 haplotype and anxiety in female anorexia nervosa.
abstract: Dehydroepiandrosterone (DHEA), the main brain neurosteroid, has been implicated in various psychiatric disorders especially those including gender differences. We studied genetic variability in the DHEA-producing enzyme CYP17A1 in relation to anorexia nervosa (AN) susceptibility and AN-related co-morbidities. We performed analysis of 100 Israeli AN family trios accounting for CYP17A1 haplotypes characteristic of populations of European origin and studied genotype-phenotype relationships using correlation analyses and transmission disequilibrium test. Although our analysis revealed no evidence of association between CYP17A1 and AN per se, it revealed an association between specific CYP17A1 haplotypes and AN co-morbidity, specifically anxiety. We found that a common CYP17A1 haplotype (H1) was associated with higher anxiety in AN patients (Clinical Global Impression; CGI-anxiety ≥4). Moreover, H1 homozygotes were at higher risk for expressing high CGI-anxiety levels (OR = 3.7), and H1 was preferentially transmitted to AN patients with high CGI-anxiety levels (P = 0. 037). We suggest that CYP17A1 H1 haplotype may contribute to genetic predisposition to higher CGI-anxiety levels in AN patients and that this predisposition may be mediated by reduced CYP17A1 enzymatic activity and corresponding lower DHEA production.
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel, efrat30.3@gmail.com.
authors.forename: Efrat
authors.initials: E
authors.lastname: Czerniak
authors.forename: Michael
authors.initials: M
authors.lastname: Korostishevsky
authors.forename: Amos
authors.initials: A
authors.lastname: Frisch
authors.forename: Yoram
authors.initials: Y
authors.lastname: Cohen
authors.forename: Ninette
authors.initials: N
authors.lastname: Amariglio
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
authors.forename: Elena
authors.initials: E
authors.lastname: Michaelovsky
authors.forename: Daniel
authors.initials: D
authors.lastname: Stein
authors.forename: Yardena
authors.initials: Y
authors.lastname: Danziger
authors.forename: Silvana
authors.initials: S
authors.lastname: Fennig
authors.forename: Alan
authors.initials: A
authors.lastname: Apter
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
authors.forename: Eva
authors.initials: E
authors.lastname: Gak
mesh_terms: D000856:Anorexia Nervosa / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology*; D001007:Anxiety / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology*; D015897:Comorbidity; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007557:Israel / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
chemical_list: C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase