Genetic association between the DRD4 promoter polymorphism and clozapine-induced sialorrhea

Veera Manikandan; Lakshmikirupa Sundaresan; A.P. Rajkumar; Chithra Chittybabu; Anju Kuruvilla; Alok Srivastava; Poonkuzhali Balasubramanian; Kuruthukulangara S. Jacob; Molly Jacob

doi:10.1097/YPG.0000000000000058

Genetic association between the DRD4 promoter polymorphism and clozapine-induced sialorrhea

Veera Manikandan^*, Lakshmikirupa Sundaresan, A.P. Rajkumar, Chithra Chittybabu, Anju Kuruvilla, Alok Srivastava, Poonkuzhali Balasubramanian, Kuruthukulangara S. Jacob, Molly Jacob

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

The use of clozapine, an effective antipsychotic drug used in treatment-resistant schizophrenia, is associated with adverse effects. Sialorrhea is one such effect, which can be distressing for many patients. Studies on the pharmacogenetics of the adverse effects of clozapine are limited. The aim of the present study was to determine whether clozapine-induced sialorrhea is associated with a 120 base-pairs (bp) tandem duplication polymorphism in the dopamine receptor subtype D4 (DRD4) gene. Ninety-five patients, mean age 35.43±9.43 years, with treatment-resistant schizophrenia and on clozapine were included in the study. Development of sialorrhea in response to the drug, as manifested by drooling of saliva, was documented in 45 (47.4%) patients. Genotyping of the patients was carried out to detect the presence of the polymorphism of interest. Clozapine-induced sialorrhea was found to be associated significantly with the 120-bp duplication in DRD4. The association was found to fit a log-additive model with an odds ratio of 2.95 (95% confidence interval 1.51–5.75; P=0.0006). Thus, the presence of the 120-bp duplication in DRD4 appears to confer a risk for sialorrhea in response to clozapine therapy. The underlying pathophysiology and clinical significance of this phenomenon warrant further investigation.

Original language	English
Journal	Psychiatric Genetics
Volume	24
Issue	6
Pages (from-to)	273-276
ISSN	0955-8829
DOIs	https://doi.org/10.1097/YPG.0000000000000058
Publication status	Published - 2014

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@article{61525ec7da9d4e8092302d8c985132c1,

title = "Genetic association between the DRD4 promoter polymorphism and clozapine-induced sialorrhea",

abstract = "The use of clozapine, an effective antipsychotic drug used in treatment-resistant schizophrenia, is associated with adverse effects. Sialorrhea is one such effect, which can be distressing for many patients. Studies on the pharmacogenetics of the adverse effects of clozapine are limited. The aim of the present study was to determine whether clozapine-induced sialorrhea is associated with a 120 base-pairs (bp) tandem duplication polymorphism in the dopamine receptor subtype D4 (DRD4) gene. Ninety-five patients, mean age 35.43±9.43 years, with treatment-resistant schizophrenia and on clozapine were included in the study. Development of sialorrhea in response to the drug, as manifested by drooling of saliva, was documented in 45 (47.4%) patients. Genotyping of the patients was carried out to detect the presence of the polymorphism of interest. Clozapine-induced sialorrhea was found to be associated significantly with the 120-bp duplication in DRD4. The association was found to fit a log-additive model with an odds ratio of 2.95 (95% confidence interval 1.51–5.75; P=0.0006). Thus, the presence of the 120-bp duplication in DRD4 appears to confer a risk for sialorrhea in response to clozapine therapy. The underlying pathophysiology and clinical significance of this phenomenon warrant further investigation.",

author = "Veera Manikandan and Lakshmikirupa Sundaresan and A.P. Rajkumar and Chithra Chittybabu and Anju Kuruvilla and Alok Srivastava and Poonkuzhali Balasubramanian and Jacob, {Kuruthukulangara S.} and Molly Jacob",

year = "2014",

doi = "10.1097/YPG.0000000000000058",

language = "English",

volume = "24",

pages = "273--276",

journal = "Psychiatric Genetics",

issn = "0955-8829",

publisher = "Lippincott Williams and Wilkins",

number = "6",

}

Genetic association between the DRD4 promoter polymorphism and clozapine-induced sialorrhea. / Manikandan, Veera; Sundaresan, Lakshmikirupa; Rajkumar, A.P. et al.
In: Psychiatric Genetics, Vol. 24, No. 6, 2014, p. 273-276.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Genetic association between the DRD4 promoter polymorphism and clozapine-induced sialorrhea

AU - Manikandan, Veera

AU - Sundaresan, Lakshmikirupa

AU - Rajkumar, A.P.

AU - Chittybabu, Chithra

AU - Kuruvilla, Anju

AU - Srivastava, Alok

AU - Balasubramanian, Poonkuzhali

AU - Jacob, Kuruthukulangara S.

AU - Jacob, Molly

PY - 2014

Y1 - 2014

N2 - The use of clozapine, an effective antipsychotic drug used in treatment-resistant schizophrenia, is associated with adverse effects. Sialorrhea is one such effect, which can be distressing for many patients. Studies on the pharmacogenetics of the adverse effects of clozapine are limited. The aim of the present study was to determine whether clozapine-induced sialorrhea is associated with a 120 base-pairs (bp) tandem duplication polymorphism in the dopamine receptor subtype D4 (DRD4) gene. Ninety-five patients, mean age 35.43±9.43 years, with treatment-resistant schizophrenia and on clozapine were included in the study. Development of sialorrhea in response to the drug, as manifested by drooling of saliva, was documented in 45 (47.4%) patients. Genotyping of the patients was carried out to detect the presence of the polymorphism of interest. Clozapine-induced sialorrhea was found to be associated significantly with the 120-bp duplication in DRD4. The association was found to fit a log-additive model with an odds ratio of 2.95 (95% confidence interval 1.51–5.75; P=0.0006). Thus, the presence of the 120-bp duplication in DRD4 appears to confer a risk for sialorrhea in response to clozapine therapy. The underlying pathophysiology and clinical significance of this phenomenon warrant further investigation.

AB - The use of clozapine, an effective antipsychotic drug used in treatment-resistant schizophrenia, is associated with adverse effects. Sialorrhea is one such effect, which can be distressing for many patients. Studies on the pharmacogenetics of the adverse effects of clozapine are limited. The aim of the present study was to determine whether clozapine-induced sialorrhea is associated with a 120 base-pairs (bp) tandem duplication polymorphism in the dopamine receptor subtype D4 (DRD4) gene. Ninety-five patients, mean age 35.43±9.43 years, with treatment-resistant schizophrenia and on clozapine were included in the study. Development of sialorrhea in response to the drug, as manifested by drooling of saliva, was documented in 45 (47.4%) patients. Genotyping of the patients was carried out to detect the presence of the polymorphism of interest. Clozapine-induced sialorrhea was found to be associated significantly with the 120-bp duplication in DRD4. The association was found to fit a log-additive model with an odds ratio of 2.95 (95% confidence interval 1.51–5.75; P=0.0006). Thus, the presence of the 120-bp duplication in DRD4 appears to confer a risk for sialorrhea in response to clozapine therapy. The underlying pathophysiology and clinical significance of this phenomenon warrant further investigation.

U2 - 10.1097/YPG.0000000000000058

DO - 10.1097/YPG.0000000000000058

M3 - Journal article

C2 - 25304228

AN - SCOPUS:84916236725

SN - 0955-8829

VL - 24

SP - 273

EP - 276

JO - Psychiatric Genetics

JF - Psychiatric Genetics

IS - 6

ER -

Genetic association between the DRD4 promoter polymorphism and clozapine-induced sialorrhea

Abstract

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