A dopamine D2 receptor gene-related polymorphism is associated with schizophrenia in a Spanish population isolate

Abstract

Numerous lines of evidence have highlighted the involvement of the dopamine system in the pathophysiology of schizophrenia. Association studies of dopaminergic genes such as the dopamine D2 receptor gene (DRD2), however, have produced contradictory results. To test the hypothesis that DRD2 polymorphisms are associated with schizophrenia, we investigated two DRD2-related polymorphisms (TaqI A1/A2 or rs1800497 and -141-C Ins/Del or rs1799732) in a Spanish population isolate from northern Spain consisting of 165 controls and 119 patients with schizophrenia. The TaqI A1 allele was less frequent in schizophrenic patients than in controls (P=0.002). A similar association was found for the TaqI A2/A2 genotype (P=0.0003). No association was found for the DRD2 -141-C Ins/Del polymorphism. The strong association between a potentially functional polymorphism, downstream of the DRD2 gene and schizophrenia, suggests that the direct or indirect functional effects of this polymorphism, acting on either the ANKK1 or DRD2 genes, may play a role in the pathophysiology of schizophrenia.

Dopamine D2 receptor gene polymorphisms and response to cabergoline therapy in patients with prolactin-secreting pituitary adenomas

“…[9][10][11][12][13][14][22][23][24][25][26] By genotyping about 200 controls and patients with prolactinomas, we found similar allelic frequencies of TaqI A1/A2, TaqI B1/B2, HphI G/T and NcoI C/T in the two groups that were comparable to those of European and American populations (NCBI, Entrez SNP database, TaqI A: http:// www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs ¼ 1800497; TaqI B: http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs ¼ 1079597; HphI:…”

“…Due to the critical role of dopaminergic activity in the central nervous system, several studies examined the association between common polymorphisms of the DRD2 gene and behavioral traits, psychiatric and neurological diseases, such as schizophrenia, alcoholism, smoking, opioids and polysubstance abuse, and susceptibility to migraine. [9][10][11][12][13][14] Accordingly, in vivo evidence supporting the potential functional significance of DRD2 variants has been accumulating. In particular, previous studies reported the association of DRD2 TaqI A, TaqI B and NcoI polymorphisms with modifications in D2 receptor binding and expression in human central nervous system, particularly in the striatum.…”

The Physiology, Signaling, and Pharmacology of Dopamine Receptors

“…Although no conclusive association has been found thus far, there are several indications that polymorphisms could contribute to the pathogenesis of the disorder or to the response to pharmacological treatments. For example, variants in the D2, D3, and D4 dopamine receptor genes have been linked to schizophrenia or to the response to antipsychotic treatments (Parsons et al, 2007;Bertram, 2008;Rondou et al, 2010), DRD4 and DRD5 have been consistently linked to candidate genes for ADHD (Coghill and Banaschewski, 2009;Gizer et al, 2009), and the D2 dopamine receptor gene has been associated with substance abuse (Le Foll et al, 2009), prolactin-secreting pituitary adenomas (Filopanti et al, 2010), and several other conditions. However, as noted by Wong et al (2000), "while there is some evidence that polymorphisms and mutations in dopamine receptors can alter functional activity and pharmacological profiles, no conclusive data link these gene variants to drug response or disease."…”

A role for Akt and glycogen synthase kinase-3 as integrators of dopamine and serotonin neurotransmission in mental health

“…For example, several genetic studies have focused on the role of DA receptor dysfunction in human disorders. [13][14][15][16][17][18] However, as noted in 2000 by Wong and colleagues, 19 "while there are some evidences that polymorphisms and mutations in [DA] receptors can alter functional activity and pharmacological profiles, no conclusive data link these gene variants to drug response or disease." Unfortunately, this situation has not changed much over the past 10 years.…”