Nucleotide sequence variation within the human tyrosine kinase B neurotrophin receptor gene: association with antisocial alcohol dependence.
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<or=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.
Xu
K
K
Sections on Molecular Genetics and Human Genetics, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
Anderson
T R
TR
Neyer
K M
KM
Lamparella
N
N
Jenkins
G
G
Zhou
Z
Z
Yuan
Q
Q
Virkkunen
M
M
Lipsky
R H
RH
D024506:5' Flanking Region; D000437:Alcoholism / Q000201:enzymology / Q000235:genetics*; D000987:Antisocial Personality Disorder / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005091:Exons; D005387:Finland; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008126:Lod Score; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D020813:Receptor, trkB / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics*
D020813:Receptor, trkB