Background: It is well established that COMT is a strong candidate gene for substance use disorder and\r\nschizophrenia. Recently we identified two SNPs in COMT (rs4680 and rs165774) that are associated with\r\nschizophrenia in an Australian cohort. Individuals with schizophrenia were more than twice as likely to carry the\r\nGG genotype compared to the AA genotype for both the rs165774 and rs4680 SNPs. Association of both rs4680\r\nand rs165774 with substance dependence, a common comorbidity of schizophrenia has not been investigated.\r\nMethods: To determine whether COMT is important in substance dependence, rs165774 and rs4680 were\r\ngenotyped and haplotyped in patients with nicotine, alcohol and opiate dependence.\r\nResults: The rs165774 SNP was associated with alcohol dependence. However, it was not associated with nicotine\r\nor opiate dependence. Individuals with alcohol dependence were more than twice as likely to carry the GG or AG\r\ngenotypes compared to the AA genotype, indicating a dominant mode of inheritance. The rs4680 SNP showed a\r\nweak association with alcohol dependence at the allele level that did not reach significance at the genotype level\r\nbut it was not associated with nicotine or opiate dependence. Analysis of rs165774/rs4680 haplotypes also revealed\r\nassociation with alcohol dependence with the G/G haplotype being almost 1.5 times more common in alcoholdependent\r\ncases.\r\nConclusions: Our study provides further support for the importance of the COMT in alcohol dependence in\r\naddition to schizophrenia. It is possible that the rs165774 SNP, in combination with rs4680, results in a common\r\nmolecular variant of COMT that contributes to schizophrenia and alcohol dependence susceptibility. This is\r\npotentially important for future studies of comorbidity. As our participant numbers are limited our observations\r\nshould be viewed with caution until they are independently replicated.
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