Abstract
To identify sequence variants in genes that may have roles in neuronal responses to alcohol, we resequenced the 5′ region of tyrosine kinase B neurotrophin receptor gene (NTRK2) and determined linkage disequilibrium (LD) values, haplotype structure, and performed association analyses using 43 single nucleotide polymorphisms (SNPs) covering the entire NTRK2 region in a Finnish Caucasian sample of 229 alcohol-dependent subjects with antisocial personality disorder (ASPD) and 287 healthy controls. Individually, three SNPs were associated with alcohol dependence and alcohol abuse (AD) (P-value from 0.0019 to 0.0059, significance level was set at P⩽0.01 corrected for multiple testing), whereas a common 18 locus haplotype within the largest LD block of NTRK2, a 119-kb region containing the 5′ flanking region and exons 1–15, was marginally overrepresented in control subjects compared to AD individuals (global P=0.057). Taken together, these results support a role for the NTRK2 gene in addiction in a Caucasian population with AD and a subtype of ASPD.
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Acknowledgements
This study was supported by intramural research grant Z01-AA00325 from the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health (RHL).
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The URLs for data presented herein are as follows:
dbSNP, http://www.ncbi.nlm.nih.gov/SNP
Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim
HapMap Project, http://www.hapmap.org
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Xu, K., Anderson, T., Neyer, K. et al. Nucleotide sequence variation within the human tyrosine kinase B neurotrophin receptor gene: association with antisocial alcohol dependence. Pharmacogenomics J 7, 368–379 (2007). https://doi.org/10.1038/sj.tpj.6500430
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DOI: https://doi.org/10.1038/sj.tpj.6500430
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