A new susceptibility gene in patients with schizophrenia?
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Date
1998
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Abstract
We have investigated the polymorphic N-acetyltransferase 2 gene (NAT2) from male patients with schizophrenia and controls of Caucasian origin. The diagnosis of schizophrenia is followed according to the DSM III-R characteristics. Since purified NAT enzyme (EC 2.3.1.5) is said to be involved in serotonm metabolism we identified six point mutations of the NAT2 gene leading to eight different alleles and 36 possible genotypes. From patients with schizophrenia, 43.5% were slow acetylators compared to 56.2% of controls, indicating that rapid acetylators could have a higher risk to develop schizophrenia. In addition, we have analyzed the human serotonin-N-acetyltransferase (aa-NAT, EC 2.3.1.87). The aa-NAT, the rate-limiting enzyme in melatonin synthesis, catalyzes the step from serotonin to N-acetylserotonin and controls the night/day rhythm in melatonin production. Since there are some studies of serotonin receptor genes in schizophrenia published in the last years, there haven't been any researches about the relevance of a possible genetic polymorphism of serotonin acetylation. The human serotonin-NAT gene spans 2.550 bp and contains four exons and three introns and is located on chromosome 17q25. The four exons have been separately amplified, isolated, and finally sequenced. As a result of sequencing, we found two point mutations, which are located at positions 2164 (G→A; Ala→Thr) and 2247 (C→T; silent) in the fourth exon of the AA-NAT gene. Furthermore, to detect these point mutations in a great number of patients we have developed a simple PCR/RFLP assay.