Positive association between SAT‐1 −1415T/C polymorphism and anxiety

Abstract

Limbic glutamatergic neurotransmission plays a pivotal role in the pathogenesis of anxiety disorders. Polyamines modulate the activity of several ionotropic glutamate receptors and have been involved in the regulation of fear-conditioning response. Spermidine/spermine N1-acetyltransferase (SSAT-1) is the main enzyme regulating polyamine catabolism. The aim of the present study was to examine the association between anxiety disorders and the -1415T/C (rs1960264) single nucleotide polymorphism (SNP) of the gene (SAT1) coding for SSAT-1. A case-control design was used in order to compare the genotypes for the -1415T/C (rs1960264) SNP between anxiety patients (n = 218), other non-anxiety psychiatric patients (n = 362), and healthy controls (n = 251). DSM-IV diagnoses were provided using MINI 4.4. Genomic DNA was extracted from peripheral blood samples collected from participants. In males, there was a significant difference in the distribution of the two genotypes (T and C) for the SAT-1 -1415T/C SNP between anxiety patients, non-anxiety psychiatric controls, and healthy controls. The T genotype was significantly more frequent in males suffering from anxiety disorders than in male psychiatric controls and healthy controls. This is the first study linking polymorphic variants of genes involved in polyamine metabolism with anxiety disorders.

Putative association between the -1415 T/C polymorphism of spermidine/spermine N1-acetyltransferase (SSAT1) gene and alcohol use disorders in women and men

“…The effect of other potential confounding factors, such as age or alcohol consumption, was not investigated. The population that we have investigated in a previous study (12) showed similar genotypic frequencies of SSAT1. However, due to missing values in the diagnosis of AUD, we were unable to assess the relationship of AUD to SSAT1 genotypic frequencies in this previous sample.…”

“…Genetics analysis was performed following the method previously described by our group (12). Briefly, PCR amplification of a 298 bp fragment from the promoter region of the SSAT1 gene containing the -1415 T/C polymorphism (rs1960264) was carried out.…”

“…Moreover, several Single Nucleotide Polymorphisms (SNP) situated near the polyamine-responsive element (PRE) of the SSAT1 gene have been studied with regards to psychopathology (rs61511267, rs6526342, rs1960264, rs2532624 and rs928931). One of them, rs6526342, was associated with depression and suicide (8,11), and another one, rs1960264, with anxiety disorders (12). This paper examined the relationship between the -1415 T/C polymorphism (rs1960264) in the SSAT1 gene and the diagnoses of alcohol use disorders (AUD).…”

Association of the SAT1 in/del polymorphism with suicide completion

“…Neuropsychiatric Genetics [Vaquero-Lorenzo et al, 2008]. One of these variants, rs6926342, was also found to be associated with SAT1 expression in several brain regions.…”

“…Moreover, as the D allele is on the same haplotype as the C risk allele of rs6526342, our results add further weight to the importance of this haplotype in suicide completion. Interestingly, this haplotype also includes the T allele of rs1960264, which has been found to be significantly associated with anxiety disorders [Vaquero-Lorenzo et al, 2008]. Given the high LD among promoter variants, these associations may all reflect the involvement of a single polymorphism in increasing the susceptibility to suicide and anxiety.…”