Pharmacogenetics of antipsychotic-induced side effects

Currently available antipsychotic drugs (APDs) carry significant though highly variable, liability to neurologic and metabolic side effects. Pharmacogenetics approaches offer the possibility of identifying patient-specific biomarkers for predicting risk of these side effects. To date, a few single nucleotide polymorphisms (SNPs) in a handful of genes have received convergent support across multiple studies. The primary focus has been on SNPs in dopamine and serotonin receptor genes: persuasive meta-analytic evidence exists for an effect of the dopamine D2 and D3 receptor genes (DRD2 and DRD3) in risk for tardive dyskinesia (TD) and for an effect of variation at the 5-HT2C receptor gene (HTR2C) for liability to APD-induced weight gain. However, effect sizes appear to be modest, and pharmacoeconomic considerations have not been sufficiently studied, thereby limiting clinical applicability at this time. Effects of these genes and others on risk for TD, extrapyramidal side effects, hyperprolactinemia, and weight gain are reviewed in this article.

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Two newly detected mutations and four new single nucleotide polymorphisms in the promotor region of exon 1 of the human growth hormone receptor gene in adult patients with growth hormone deficiency

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-2005-920449 ◽

2005 ◽

Vol 113 (08) ◽

Author(s):

S Meyer ◽

M Arnken ◽

A Keth ◽

PH Kann

Keyword(s):

Growth Hormone ◽

Growth Hormone Receptor ◽

Receptor Gene ◽

Human Growth ◽

Hormone Deficiency ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Exon 1 ◽

Growth Hormone Receptor Gene ◽

Human Growth Hormone Receptor

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Single nucleotide polymorphisms in the progesterone receptor gene and association with uterine leiomyoma tumor characteristics and disease risk

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2008.06.015 ◽

2008 ◽

Vol 199 (6) ◽

pp. 648.e1-648.e9 ◽

Cited By ~ 9

Author(s):

Stefan P. Renner ◽

Reiner Strick ◽

Peter A. Fasching ◽

Sonja Oeser ◽

Peter Oppelt ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Progesterone Receptor ◽

Uterine Leiomyoma ◽

Disease Risk ◽

Receptor Gene ◽

Tumor Characteristics ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Progesterone Receptor Gene

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Correlating single nucleotide polymorphisms in the myostatin gene with performance traits in rabbit

World Rabbit Science ◽

10.4995/wrs.2016.4026 ◽

2016 ◽

Vol 24 (3) ◽

pp. 213 ◽

Cited By ~ 1

Author(s):

E.M. Abdel-Kafy ◽

S.F. Darwish ◽

D. ElKhishin

Keyword(s):

Body Weight ◽

Weight Gain ◽

Single Nucleotide Polymorphisms ◽

Untranslated Region ◽

Carcass Traits ◽

Reproductive Traits ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Mstn Gene ◽

Positive Effects

The Myostatin (MSTN), or Growth and Differentiation Factor 8 (GDF8), gene has been implicated in the double muscling phenomenon, in which a series of mutations render the gene inactive and unable to properly regulate muscle fibre deposition. Single nucleotide polymorphisms (SNPs) in the MSTN gene have been correlated to production traits, making it a candidate target gene to enhance livestock and fowl productivity. This study aimed to assess any association of three SNPs in the rabbit MSTN gene (c.713T>A in exon 2, c.747+34C>T in intron 2, and c.*194A>G in 3’-untranslated region) and their combinations, with carcass, production and reproductive traits. The investigated traits included individual body weight, daily body weight gain, carcass traits and reproductive traits. The 3 SNPs were screened using PCR-restriction fragment length polymorphism (RFLP)-based analysis and the effects of the different SNP genotypes and their combinations were estimated in a rabbit population. Additionally, additive and dominance effects were estimated for significant traits. The results found no significant association between the c.713 T>A SNP and all the examined traits. Allele T at the c.747+34C>T SNP was only significantly associated (P<0.05) with increased body weight at 12 wk of age. However, for the SNP residing in the 3’ untranslated region (c.*194A>G), allele G was significantly associated (P<0.05) with increased body weight and high growth rate. Genotype GG at the c.*194A>G SNP also had positive effects on most carcass traits. The estimated additive genetic effect for the c.*194A>G SNP was significant (P<0.05) with most body weight, daily gain and carcass traits. No significant association was obtained between any MSTN SNPs and reproductive traits. In the combinations analysis, regardless of the genotypes of SNPs at c.713T>A and c.747+34C>T, GG at the c.*194A>G SNP correlated with highest values in body weight and daily weight gain. In conclusion, the ‘G’ allele at the c.*194A>G SNP had positive effects on growth and carcass traits and so could be used as a favourable allele in planning rabbit selection. Further population-wide studies are necessary to test the association of the c.*194A>G SNP with carcass traits. We also recommend evaluation of the potential effects of the c.*194A>G SNP on MSTN gene expression.

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Characterisation of the melanocortin-1 receptor gene in alpaca and identification of possible markers associated with phenotypic variations in colour

Animal Production Science ◽

10.1071/an09005 ◽

2009 ◽

Vol 49 (8) ◽

pp. 675 ◽

Cited By ~ 21

Author(s):

N. L. Feeley ◽

K. A. Munyard

Keyword(s):

Mus Musculus ◽

Bos Taurus ◽

Receptor Gene ◽

Nucleotide Polymorphisms ◽

Wild Type ◽

Single Nucleotide ◽

Melanocortin 1 Receptor ◽

Mc1r Gene ◽

Pcr Products ◽

Phenotypic Variations

The aim of this study was to determine if any correlation exists between melanocortin-1 receptor (MC1R) polymorphisms and skin and fibre colour in alpacas. Primers capable of amplifying the entire alpaca MC1R gene were designed from a comparative alignment of Bos taurus and Mus musculus MC1R gene sequences. The complete MC1R gene of 41 alpacas exhibiting a range of fibre colours, and which were sourced from farms across Australia, was sequenced from PCR products. Twenty-one single nucleotide polymorphisms were identified within MC1R. Two of these polymorphisms (A82G and C901T) have the potential to reduce eumelanin production by disrupting the activity of MC1R. No agreement was observed between fibre colour alone and MC1R genotype in the 41 animals in this study. However, when the animals were assigned to groups based on the presence or absence of eumelanin in their fibre and skin, only animals that had at least one allele with the A82/C901 combination expressed eumelanin. We propose that A82/C901 is the wild-type dominant ‘E’ MC1R allele, while alpacas with either G82/T901 or G82/Y901 are homozygous for the recessive ‘e’ MC1R allele and are therefore unable to produce eumelanin.

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Single Nucleotide Polymorphisms Identification and Genotyping Analysis of Melanocortin 1 Receptor Gene in Various Plumage Colours Magelang Ducks

International Journal of Poultry Science ◽

10.3923/ijps.2015.207.212 ◽

2015 ◽

Vol 14 (4) ◽

pp. 207-212 ◽

Cited By ~ 5

Author(s):

Ayu Rahayu ◽

Dattadewi Purwantini ◽

Dyah Maharani ◽

Tety Hartatik

Keyword(s):

Single Nucleotide Polymorphisms ◽

Receptor Gene ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Melanocortin 1 Receptor

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Histamine H3 receptor gene variants associated with drug abuse in patients with cocaine use disorder

Journal of Psychopharmacology ◽

10.1177/0269881120961253 ◽

2020 ◽

Vol 34 (11) ◽

pp. 1326-1330

Author(s):

Iñigo Pallardo-Fernández ◽

José Ramón Muñoz-Rodríguez ◽

Carmen González-Martín ◽

Luis F Alguacil

Keyword(s):

Drug Abuse ◽

Single Nucleotide Polymorphisms ◽

Receptor Gene ◽

Gene Variants ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Histamine H3 Receptor ◽

Cocaine Use ◽

H3 Receptor ◽

Histamine H3

Background: Preclinical work revealed significant interactions between ligands of the histamine H3 receptor and different drugs of abuse. In the case of psychostimulants, the results reported are somewhat controversial and human data are still scarce, despite the fact that an inverse agonist of the H3 receptor (pitolisant) has reached the market after approval for the treatment of narcolepsy. Aims: We have studied associations between histamine H3 receptor gene variants and cocaine use disorder to increase the knowledge of the possible involvement of histamine H3 receptor in drug abuse. Methods: Seven single nucleotide polymorphisms of the histamine H3 receptor gene were genotyped by using a multiplexing assay in 248 samples of subjects with cocaine use disorder and 500 randomized samples of subjects representative of the Spanish population. Results: The study of the epidemiological information associated to the samples revealed that subjects with cocaine use disorder broadly abused alcohol, tobacco and cannabinoids. Two single nucleotide polymorphisms (rs3787430 and rs74627870) were found significantly associated with the occurrence of addiction and one more (rs13042865) was specifically related to the severity of cocaine dependence within drug abusers. Conclusions: The associations found in this study further extend the hypothesis that histamine H3 receptor function could be relevant in drug abuse in general and cocaine addiction in particular.

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