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No association of alcohol dependence with HOMER 1 and 2 genetic variants
Author(s) -
Preuss U.W.,
Ridinger M.,
Rujescu D.,
Fehr C.,
Koller G.,
Wodarz N.,
Bondy B.,
Soyka M.,
Wong W.M.,
Zill P.
Publication year - 2010
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.31074
Subject(s) - haplotype , linkage disequilibrium , single nucleotide polymorphism , genetics , alcohol dependence , biology , snp , phenotype , genetic association , neurochemical , glutamate receptor , allele , alcohol , gene , genotype , neuroscience , receptor , biochemistry
Several lines of evidence indicate that alterations of the central cortico‐accumbens glutamate pathway are involved in the development and maintenance of alcohol‐ and substance‐use disorders. The HOMER protein family is encoded by 3 genes HOMER (1–3) which are components of the excitatory postsynaptic density complex and function to modulate synaptic activity by the regulation of glutamate signaling. HOMER 1 and 2 have been reported to contribute to chronic alcohol‐induced long‐term neurochemical changes in the endogenous reward system. Data from animal models suggest a potential role of the Homer protein family in the development of alcohol and substance use. The aim of this study is to assess potential associations between HOMER 1 and 2 genetic variants in a larger sample of alcohol‐dependent individuals and unrelated controls. Five genetic variants of HOMER 1 and 3 of HOMER 2 were genotyped in a multi‐site sample of 1,923 German healthy controls and 2,039 alcohol‐dependent subjects. Neither single SNP nor haplotype analysis could detect significant associations with alcohol dependence (AD) and related phenotypes. While most of the HOMER 1 and 2 SNPs are in low‐to‐moderate linkage disequilibrium, three major haplotypes of HOMER 1 and 4 haplotypes of HOMER 2 are present in the majority of alcohol‐dependent and control subjects. In conclusion, our results suggest that single SNPs, respectively, haplotypes of the HOMER 1 and 2 genes are unlikely to play a major role in the pathophysiology of AD. © 2010 Wiley‐Liss, Inc.