b4f80653-bc09-422b-89cc-6ac4ffe55592
title
Variants in the  catechol-o-methyltransferase  ( COMT ) gene are associated with schizophrenia in Irish high-density families.
efe5f315-698a-4b31-9ebc-2f113f2a0964
abstract
The enzyme  catechol-o-methyltransferase  ( COMT ) transfers a methyl group from adenosylmethionine to catecholamines including the neurotransmitters dopamine, epinephrine and norepinephrine. This methylation results in the degradation of catecholamines. The involvement of the  COMT  gene in the metabolic pathway of these neurotransmitters has made it an attractive candidate gene for many psychiatric disorders. In this article, we reported our study of association of  COMT  with schizophrenia in Irish families with a high density of schizophrenia. Three single nucleotide polymorphisms (SNPs) were genotyped for the 274 such families and within-family transmission disequilibrium tests were performed. SNP  rs4680 , which is the functional Val/Met polymorphism, showed modest association with the disease by the TRANSMIT, FBAT and PDT programs, while the other two SNPs were negative. These SNPs showed lower level of LDs with each other in the Irish subjects than in Ashkenazi Jews. Haplotype analysis indicated that a haplotype, haplotype A-G-A for SNPs  rs737865 - rs4680 - rs165599 , was preferentially transmitted to the affected subjects. This was different from the reported G-G-G haplotype found in Ashkenazi Jews, but both haplotypes shared the Val allele. We concluded that  COMT  gene is associated with schizophrenia and carries a small but significant risk to the susceptibility in the Irish subjects.