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Receptor Subunit Gene (receptor + subunit_gene)

Distribution by Scientific Domains

Life Sciences	60%

Selected Abstracts

Association of Markers in the 3, Region of the GluR5 Kainate Receptor Subunit Gene to Alcohol Dependence

ALCOHOLISM, Issue 5 2009
Henry R. Kranzler
Background:, Glutamate neurotransmission plays an important role in a variety of alcohol-related phenomena, including alcohol self-administration by both animals and humans. Because the risk for alcohol dependence (AD) is genetically influenced, genes encoding glutamate receptors are candidates to contribute to the risk for AD. We examined the role of variation in the 3, region of GRIK1, the gene that encodes the GluR5 receptor subunit of the kainic acid glutamate receptor, on risk for AD. We focused specifically on this gene because topiramate, a glutamate modulator that binds to the GluR5 subunit, has shown robust efficacy in the treatment of AD. Methods:, We genotyped 7 single nucleotide polymorphisms (SNPs) in the 3,-half of GRIK1, which includes 3 differentially spliced exons, in a sample of EA control subjects (n = 507) and subjects with AD (n = 1,057). Results:, We found nominally significant evidence of association to AD for 3 SNPs (rs2832407 in intron 9, rs2186305 in intron 17, and rs2832387 in the 3,UTR). Empirical p -value estimation revealed that only rs2832407 was significantly associated to phenotype (p = 0.043). Discussion:, These findings provide support for the hypothesis that variation in the 3, portion of the gene encoding the GluR5 kainate receptor subunit contributes to the risk for AD. Further research is needed to ascertain whether this SNP is itself functional or whether the association reflects linkage disequilibrium with functional variation elsewhere in the gene and whether this SNP moderates topiramate's effects in the treatment of AD. [source]

Deletion of the ,7 Nicotinic Receptor Subunit Gene Results in Increased Sensitivity to Several Behavioral Effects Produced by Alcohol

ALCOHOLISM, Issue 3 2005
Barbara J. Bowers
Background: The finding that most people with alcoholism are also heavy smokers prompted several research groups to evaluate the effects of ethanol on neuronal nicotinic acetylcholine receptor (nAChR) function. Data collected in vitro indicate that physiologically relevant concentrations of ethanol inhibit the functional activation of homomeric ,7 nAChRs, which are one of the most abundant nAChR subtypes expressed in the mammalian brain. The studies outlined here used ,7 gene knockout (null mutant) mice to evaluate the potential role of ,7 nAChRs in modulating selected behavioral and physiological effects produced by ethanol. Methods: Current evidence indicates that many responses to ethanol are not genetically correlated. Therefore, the authors measured the effects of acute administration of ethanol on several behaviors that are altered by both ethanol and nicotine: two tests of locomotor activity, acoustic startle, prepulse inhibition of acoustic startle, and body temperature. Ethanol-induced durations of loss of righting reflex and ethanol elimination rates were also determined. These studies used null mutant (,7,/,) and wild-type (,7+/+) mice. Results: Relative to ,7+/+ mice, ,7,/, mice were more sensitive to the activating effects of ethanol on open-field activity, ethanol-induced hypothermia, and duration of loss of the righting response. Deletion of the ,7 gene did not influence the effects of ethanol on Y-maze crossing or rearing activities, acoustic startle, or prepulse inhibition of startle. Gene deletion did not alter ethanol metabolism. Conclusions: These results indicate that some but not all of the behavioral effects of ethanol are mediated in part by effects on nAChRs that include the ,7 subunit and may help to explain the robust association between alcohol consumption and the use of tobacco. [source]

An Analysis Paradigm for Investigating Multi-locus Effects in Complex Disease: Examination of Three GABAA Receptor Subunit Genes on 15q11-q13 as Risk Factors for Autistic Disorder.

ANNALS OF HUMAN GENETICS, Issue 3 2006
A. E. Ashley-Koch
Summary Gene-gene interactions are likely involved in many complex genetic disorders and new statistical approaches for detecting such interactions are needed. We propose a multi-analytic paradigm, relying on convergence of evidence across multiple analysis tools. Our paradigm tests for main and interactive effects, through allele, genotype and haplotype association. We applied our paradigm to genotype data from three GABAA receptor subunit genes (GABRB3, GABRA5, and GABRG3) on chromosome 15 in 470 Caucasian autism families. Previously implicated in autism, we hypothesized these genes interact to contribute to risk. We detected no evidence of main effects by allelic (PDT, FBAT) or genotypic (genotype-PDT) association at individual markers. However, three two-marker haplotypes in GABRG3 were significant (HBAT). We detected no significant multi-locus associations using genotype-PDT analysis or the EMDR data reduction program. However, consistent with the haplotype findings, the best single locus EMDR model selected a GABRG3 marker. Further, the best pairwise genotype-PDT result involved GABRB3 and GABRG3, and all multi-locus EMDR models also selected GABRB3 and GABRG3 markers. GABA receptor subunit genes do not significantly interact to contribute to autism risk in our overall data set. However, the consistency of results across analyses suggests that we have defined a useful framework for evaluating gene-gene interactions. [source]

Genetic variation of the human glycine receptor subunit genes GLRA3 and GLRB and susceptibility to idiopathic generalized epilepsies

AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 6 2001
Diana Sobetzko
Abstract Alterations of glycine receptor ,1 and , subunit genes have been associated with hypertonic motor disorders in both mice and humans. Mutations in genes encoding other ligand- and voltage-gated ion channels have been identified in rare monogenic forms of idiopathic generalized epilepsies (IGE). We tested the hypothesis that allelic variants of the glycine receptor subunit genes, GLRA3 and GLRB, both localized on chromosome 4q, confer susceptibility to common subtypes of IGE. Mutation screening was carried out in index patients of 14 IGE families. No pathogenic mutation was found, but two intronic polymorphisms were detected in the GLRB gene, and four intronic, three exonic, and one 3,-UTR polymorphisms were identified for the GLRA3 gene. Subsequent screening for exonic and 3,-UTR polymorphisms in GLRA3 showed no statistical difference between a group of sporadic IGE patients (n,=,104) and a control group (n,=,141). The genotype frequencies for exonic and 3,-UTR polymorphisms in GLRA3 showed no statistically significant difference between IGE patients (n,=,104) and an ethnically matched control group (n,=,141). Thus, no association between IGE and alterations in GLRA3 or GLRB genes could be detected, indicating that both genes do not play a major causative role in the epileptogenesis of common IGE subtypes. Still, these novel single nucleotide polymorphisms may be useful markers for candidate gene analyses of other disorders. © 2001 Wiley-Liss, Inc. [source]

An Analysis Paradigm for Investigating Multi-locus Effects in Complex Disease: Examination of Three GABAA Receptor Subunit Genes on 15q11-q13 as Risk Factors for Autistic Disorder.