title: Association analysis of polymorphisms in serotonin 1B receptor (HTR1B) gene with heroin addiction: a comparison of molecular and statistically estimated haplotypes.
abstract: OBJECTIVE
  5-Hydroxytryptamine (serotonin)-1B receptors (HTR1B) may play an important role in psychiatric disorders and drug and alcohol dependence. In this study we report on genotype, molecular haplotype and statistically estimated haplotype analyses of previously identified polymorphisms in positions -261T>G, -161A>T, 129C>T, 861G>C and 1180A>G of the HTR1B gene in ethnically diverse populations (African-Americans, Caucasians, Hispanics and Asians) including 235 former heroin addicts and 161 control subjects from New York City. The objectives were to test for an association of molecular and statistically estimated haplotypes and genotypes in HTR1B gene with heroin addiction and to compare results provided by molecular and statistically estimated haplotyping methods.
  
  
  METHODS
  Genotype analysis was performed using a standard TaqMan protocol. Molecular haplotype analysis of the subset of polymorphisms consisting of -261T>G, -161A>T and 129C>T was performed using a protocol specially designed by our group, using fluorescent PCR. This is based on use of allele-specific primers complementary to flanking polymorphisms and a fluorescently labeled sequence-specific TaqMan probe set complementary to an internal polymorphism of the haplotype region. Every individual's statistically inferred haplotype pair agreed with the individual's haplotype pair determined by molecular haplotyping.
  
  
  CONCLUSIONS
  A point-wise significant association of haplotype pairs containing allele G at position 1180 with protective effect from heroin addiction in Caucasians was found. A point-wise nominally significant association of allele 1180G with a protective effect from heroin addiction was found in Caucasians. Statistically significant differences across four ethnic groups in control subjects for allelic frequencies of -261T>G and -161A>T were found.
authors.affiliation: Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. proudnd@mail.rockefeller.edu
authors.forename: Dmitri
authors.initials: D
authors.lastname: Proudnikov
authors.forename: K Steven
authors.initials: KS
authors.lastname: LaForge
authors.forename: Heather
authors.initials: H
authors.lastname: Hofflich
authors.forename: Mark
authors.initials: M
authors.lastname: Levenstien
authors.forename: Derek
authors.initials: D
authors.lastname: Gordon
authors.forename: Sandra
authors.initials: S
authors.lastname: Barral
authors.forename: Jurg
authors.initials: J
authors.lastname: Ott
authors.forename: Mary Jeanne
authors.initials: MJ
authors.lastname: Kreek
mesh_terms: D001741:Black or African American / Q000235:genetics; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006556:Heroin Dependence / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics*
chemical_list: D044302:Receptor, Serotonin, 5-HT1B