Dopamine transporter (DAT) genotype (VNTR) and phenotype in extrapyramidal symptoms induced by antipsychotics

Lafuente, Amàlia; Bernardo, Miquel; Mas, Sergi; Crescenti, Anna; Aparici, Mònica; Gassó, Patricia; Catalán, Rosa; Mateos, J.J.; Lomeña, Francisco; Parellada, Eduard

doi:10.1016/j.schres.2006.09.031

Cited by 44 publications

(22 citation statements)

References 30 publications

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“…Van Dyck et al found a (18,19), and the binding ratios are much higher. All the other studies that demonstrated different effects of the VNTR on striatal DAT availability (10,11,13) (13). The methodologic differences in subject population, sample size, radioligand, and outcome measures of the studies on DAT availability and DAT genotype could mainly explain the variable findings.…”

Section: Discussionmentioning

confidence: 98%

“…Two studies in healthy subjects reported significantly lower striatal DAT binding for 10R homozygotes (8,9). Studies that also included subjects with neuropsychiatric disorders showed different results: 2 showed increased striatal DAT availability for 10R homo-zygotes (10,11), and 3 found no association (12)(13)(14). Although differences in population, radioligand, and sample size can partially explain the inconsistent results, data on the specific effect of the VNTR polymorphism on striatal DAT binding in humans remain inconclusive.…”

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confidence: 99%

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Striatal Dopamine Transporter Availability Associated with Polymorphisms in the Dopamine Transporter Gene SLC6A3

Giessen¹,

Win²,

Tanck³

et al. 2008

J Nucl Med

141

110

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Polymorphisms in the dopamine transporter (DAT) gene SLC6A3 are associated with human striatal DAT expression, but the exact effects on DAT expression are not clear. A variable number of tandem repeats (VNTR) in the 39 untranslated region of the DAT gene was previously investigated in relation to striatal DAT availability, but the results were inconclusive. Other polymorphisms in the DAT gene were not extensively studied. Therefore, we investigated whether polymorphisms in both 39 and 59 ends of the DAT gene show association with in vivo striatal DAT expression. Methods: The subjects were an ethnically homogeneous group of 79 healthy young adults. Striatal DAT availability was measured with 123 I-(2-b-carbomethoxy-3-b(4-iodophenyl)-tropane) ( 123 I-b-CIT) SPECT. The 40-base-pair VNTR in the 39 untranslated region of the DAT gene and the 2 single nucleotide polymorphisms (SNPs) rs2652511 and rs2937639 in the 59 end of the DAT gene were genotyped. Multiple-regression analysis was performed for each of the 3 polymorphisms. Analysis of the combination of the polymorphisms (haplotype analysis) was conducted for the triad rs2652511-rs2937639-VNTR. Results: For the VNTR, the 9-repeat (9R) allele was associated with significantly higher striatal DAT expression than was the 10-repeat (10R) allele (P 5 0.002). Subanalysis suggested a dominant effect for the 9R allele. Neither SNP rs2652511 nor SNP rs2937639 was associated with striatal DAT availability. The haplotype T-A-9R (rs2652511-rs2937639-VNTR) was significantly more associated with higher striatal DAT expression than were the other haplotypes (P 5 0.009). Conclusion: The DAT VNTR 9R carriers have higher striatal DAT availability than do 10R homozygotes. This finding replicates former studies that included healthy subjects and also used 123 I-b-CIT SPECT. Our haplotype analysis identified a subgroup of 9R carriers, the T-A-9R, which appears to be mainly responsible for the association with higher striatal DAT availability. Thus, a combination of polymorphisms in both the 39 and the 59 ends of the DAT gene is associated with in vivo striatal DAT expression. This finding in healthy subjects may contribute to research on DAT availability and genotype in neuropsychiatric disorders.

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Section: Discussionmentioning

confidence: 98%

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confidence: 99%

Striatal Dopamine Transporter Availability Associated with Polymorphisms in the Dopamine Transporter Gene SLC6A3

Giessen¹,

Win²,

Tanck³

et al. 2008

J Nucl Med

141

110

View full text Add to dashboard Cite

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“…Effects of dopamine transporter (DAT) polymorphisms on DAT binding (Table 3) We have identified nine SPECT studies examining the association between the DAT 3′ VNTR polymorphism and DAT binding in striatum (Cheon et al, 2005;Heinz et al, 2000a;Jacobsen et al, 2000;Krause et al, 2006;Lafuente et al, 2007;Lynch et al, 2003;Martinez et al, 2001b;van de Giessen et al, 2009;van Dyck et al, 2005) (Table 3). Heinz et al (2000a) studied 25 subjects (14 abstinent patients with alcohol dependence and 11 controls) with [ 123 I]β-CIT SPECT, and found a 22% increase in mean DAT binding in putamen in subjects homozygous for the 10-repeat allele compared with 9-allele carriers.…”

Section: Dopamine Transporter Polymorphismsmentioning

confidence: 99%

“…Using [ 123 I]β-CIT and SPECT, Martinez et al (2001b) found no association between DAT binding and the DAT 3′ VNTR polymorphism in a sample of 43 subjects (22 patients (Lynch et al, 2003). A small study examining striatal DAT binding in fifteen antipsychoticnaïve patients with schizophrenia using [ 123 I] FP-CIT SPECT found no difference among 9-repeat and 10-repeat allele genotype groups (Lafuente et al, 2007). In a carefully designed study in 29 drug-naïve adult patients with ADHD from the same region in Southern Germany, Krause et al (2006) did not find an association of the DAT 3′ VNTR polymorphism and DAT binding using [ 99m Tc]TRODAT-1 SPECT.…”

Section: Dopamine Transporter Polymorphismsmentioning

confidence: 99%

Imaging the effects of genetic polymorphisms on radioligand binding in the living human brain: A review on genetic neuroreceptor imaging of monoaminergic systems in psychiatry

Willeit

Praschak-Rieder

2010

NeuroImage

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“…Furthermore, we categorized the CEDD values into three groups (high, medium and low dosage), as described earlier. 18 These strategies are commonplace in psychopharmacology and have been used in several pharmacogenetic studies. 19,20 This pharmacogenetic study revealed an association of risperidone-induced EPS with rs167771, a common genetic variant in the third intron of the DRD3 gene.…”

Section: Discussionmentioning

confidence: 99%

A common variant in DRD3 gene is associated with risperidone-induced extrapyramidal symptoms

et al. 2009

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We present a pharmacogenetic study of acute antipsychotic (AP)-induced extrapyramidal symptoms (EPS) using an extensive linkage disequilibrium mapping approach in seven-candidate genes with a well-established link to dopamine (DRD2, DRD3, ACE, COMT, DAT, MAO-A, MAO-B). From a cohort of 321 psychiatric inpatients, 81 cases presenting with EPS (Simpson-Angus 43) and 189 controls presenting without EPS (Simpson-Angus p3) took part. Eighty-four-tag single nucleotide polymorphisms (SNPs) in candidate genes were genotyped. After extensive data cleaning, 70 SNPs were analyzed for association of single markers and haplotypes. AP dosage, AP-DRD2 blockade potency and age were identified as susceptibility factors for APinduced EPS. One SNP of the DRD3 gene, rs167771, achieved significant association with EPS risk after Bonferroni correction (nominal P-value 1.3 Â 10 À4 ) in the patients treated with risperidone (132 patients). APinduced EPS remains a serious public health problem. Our finding of a common SNP (rs167771) in the DRD3 gene provides a strong new candidate gene for risperidone-induced EPS.

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Dopamine transporter (DAT) genotype (VNTR) and phenotype in extrapyramidal symptoms induced by antipsychotics

Cited by 44 publications

References 30 publications

Striatal Dopamine Transporter Availability Associated with Polymorphisms in the Dopamine Transporter Gene SLC6A3

Striatal Dopamine Transporter Availability Associated with Polymorphisms in the Dopamine Transporter Gene SLC6A3

Imaging the effects of genetic polymorphisms on radioligand binding in the living human brain: A review on genetic neuroreceptor imaging of monoaminergic systems in psychiatry

A common variant in DRD3 gene is associated with risperidone-induced extrapyramidal symptoms

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