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

Abstract

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.

Association between genetic variants related to glutamatergic, dopaminergic and neurodevelopment pathways and white matter microstructure in child and adolescent patients with obsessive–compulsive disorder

“…Interestingly, two other polymorphisms located in the same genes (SLC6A3 rs4975646 and DRD3 rs3773679) were significantly associated (after Bonferroni correction) with WM microstructure in our OCD sample, and a further three polymorphisms (SLC6A3 rs1048953, DRD3 rs2087017 and DRD3 rs167771) also showed non-significant trends (p r0.0028; data not shown). Although these polymorphisms have not previously been related to OCD, some of them have been associated with the pathophysiology or pharmacological treatment of other psychiatric disorders (Dannlowski et al, 2013, De Krom et al, 2009Gassó et al, 2009). Clinical evidence and molecular imaging studies support the involvement of dopamine in OCD.…”

DRD3 Ser9Gly Polymorphism and Its Influence on Risperidone Response in Autistic Children

“…Some reports has previously suggested this variant to be a predictor for clinical improvement with risperidone therapy (33,48) and also a parameter associated with risperidone side effects (49). On the other side, some studies suggest no significant contribution of this variant to risperidone treatment (30,50).…”

Pharmacodynamic gene polymorphism and adverse drug reactionsthen applying antipsychotic drugs

“…Следующее исследование выявило еще один значимый полиморфизм DRD3 -rs167771, который ассоциировался с экстрапирамидными расстройствами в исследовании 270 пациентов, получавших рисперидон [49], но этот резуль-тат требует дальнейшего подтверждения. Одно неболь-шое исследование показало, что на риск возникновения экстрапирамидных расстройств может оказывать влияние наличие аллели С в полиморфизме гена HTR2A (rs6313), что также соответствует результатам относительно развития поздней дискинезии [47].…”