Novel and previously reported single-nucleotide polymorphisms in the human 5-HT(1B) receptor gene: no association with cocaine or alcohol abuse or dependence.
Evidence from animal self-administration and human genetics studies suggests that the serotonin(1B) (5-HT(1B)) receptor may be involved in modulating responses to cocaine or alcohol. We hypothesize that polymorphisms, including single-nucleotide polymorphisms (SNPs), in the human 5-HT(1B) receptor gene, may be associated with individual differences in vulnerability to cocaine or alcohol abuse or dependence. A total of 210 subjects were studied, including individuals with a primary diagnosis (DSM-IV criteria) of cocaine abuse or dependence, alcohol abuse or dependence, and controls with no history of previous or current illicit drug or alcohol abuse or dependence. Genomic DNA samples were isolated from each individual. For 157 of the subjects, polymerase chain reaction (PCR) was used to amplify the entire coding region of the 5-HT(1B) receptor gene as well as parts of the 5' and 3' untranslated regions. PCR products were sequenced in forward and reverse directions on an automated sequencer. Amplified DNA from an additional 53 subjects was sequenced in the 5' untranslated region to gain additional data on the frequency of one identified SNP. Seven polymorphisms were identified: one novel SNP in the 5' untranslated region (UTR) of the gene (A-161T); one SNP not reported in any published scientific communication (but found to be recorded in GenBank) in the 3' UTR (A1180G); two novel dinucleotide deletions at positions - 184/- 183 and - 182/- 181; and three previously identified SNPs (T-261G, C129T, G861C). Data were stratified by ethnicity and pooled Relative Risk was calculated for combined alcohol abuse and dependence cases and controls, and also for combined cocaine abuse and dependence cases and controls. No significant differences between cases and controls were found.
Cigler
T
T
Laboratory of the Biology of Addictive Diseases, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
LaForge
K S
KS
McHugh
P F
PF
Kapadia
S U
SU
Leal
S M
SM
Kreek
M J
MJ
D000437:Alcoholism / Q000235:genetics; D000483:Alleles; D044383:Black People / Q000235:genetics; D019970:Cocaine-Related Disorders / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000235:genetics*; D012737:Sex Factors; D044465:White People / Q000235:genetics
C470302:HTR1B protein, human; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D004247:DNA