Archival ReportBiological Effects of COMT Haplotypes and Psychosis Risk in 22q11.2 Deletion Syndrome
Section snippets
Human Study Samples
Individuals with 22q11.2DS were recruited from the Behavioral Neurogenetics Center at a large tertiary referral center in Israel, and control subjects were taken from samples of European ancestry at the National Institute of Mental Health (see Methods in Supplement 1) (10). The study protocol was approved by the Institutional Review Board of Rabin Medical Center and the National Institute of Mental Health Institutional Review Board, and informed consent was obtained from all participants or
22q11.2DS Versus Normal Control Subjects
To compare main effects of hemizygosity, we selected a subset of 20 adult individuals with 22q11.2DS who were age and sex matched to 16 healthy adult comparison subjects (28.8 ± 6.4 years vs. 31.4 ± 8.4 years, p = .32 and male/female ratio of 10/10 vs. 7/9, p = .49, respectively). As expected, there were significant, robust differences between 22q11.2DS and control subjects in all COMT products including COMT-extended and COMT-common mRNAs, S-COMT and MB-COMT protein levels and COMT enzyme
Discussion
The principal findings of this study are as follows: 1) 22q11.2DS is associated with reduced expression of COMT gene products in peripheral cells, with individuals having approximately 50% less COMT mRNA, COMT protein expression, and enzyme activity compared with normal comparison subjects; 2) the Val158Met genotype had predicted but weak effects on COMT biology in 22q11.2DS, as previously reported in nonhemizygous individuals (14); 3) identification of haplotypes consisting of previously
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Authors DG and AJL contributed equally to the work.
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Authors DG and AJL contributed equally to the work.