Haplotype analysis of the COMT-ARVCF gene region in Israeli anorexia nervosa family trios

Elena Michaelovsky, Amos Frisch*, Shani Leor, Daniel Stein, Yardena Danziger, Cynthia Carel, Silvana Fennig, Marc Mimouni, Sabine M. Klauck, Axel Benner, Annemarie Poustka, Alan Apter, Abraham Weizman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Anorexia nervosa (AN) is a severe and complex psychiatric disorder with a significant genetic contribution. Previously, we found an association between AN and the 158Val/Met polymorphism of the catechol-O-methyltransferase (COMT) gene in a family-based study of 51 Israeli AN trios. In the present study, we extended the original sample to include 85 family trios [66 AN restricting (AN-R) and 19 bingeing/purging (AN-BP) subtype] and performed a family-based transmission disequilibrium test (TDT) analysis for five SNPs in the COMT and two in the adjacent ARVCF gene. Association was found between AN-R and several SNPs in the COMT-ARVCF region including the 158Val/Met polymorphism. TDT analysis of 5-SNP haplotypes in AN-R trios revealed an overall statistically significant transmission disequilibrium (P < 0.001). Specifically, haplotype B [COMT-186C-408G-472G(158Val)-ARVCF-659C(220Pro)-524T(175Val)] was preferentially transmitted (P < 0.001) from parents of AN-R patients to their affected daughters, while haplotype A [COMT-186T-408C-472A(158Met)-ARVCF- 659T(220Leu)-524C(175Ala)] was preferentially (P = 0.01) not transmitted. Haplotype B was associated with increased risk (RR 3.38; 0.95CI 1.98-6.43) while haplotype A exhibited a protective effect (RR 0.40; 0.95CI 0.21-0.70) for AN-R. Preferential transmission of the risk alleles and haplotypes from the parents was mostly contributed by the fathers. No significant transmission disequilibrium of alleles or haplotypes was found for AN-BP trios. The risk and protective haplotypes may carry molecular variations in the COMT gene or its vicinity that are relevant to the pathophysiology of restrictive anorexia nervosa in the Israeli-Jewish population.

Original languageEnglish
Pages (from-to)45-50
Number of pages6
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume139 B
Issue number1
StatePublished - 5 Nov 2005


  • Association
  • Bingeing/purging
  • Eating disorders
  • Restricting
  • Transmission disequilibrium test (TDT)


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