BACKGROUND: Association studies of a reportedly functional polymorphism in the promoter region (5'-HTTLPR) of the gene encoding the serotonin transporter protein (genetic locus SLC6A4) in alcoholics have yielded conflicting results. The most frequently observed alleles of the 5'-HTTLPR polymorphism are the short and long variants; the short variant is associated with lower transcriptional activity of the SLC6A4 gene than is the long variant. To reduce the heterogeneity that may confound association studies of alcohol dependence, we examined the association of 5'-HTTLPR alleles with three dichotomous typologies of alcoholism based on sex, comorbid drug dependence, or age of onset of alcohol dependence. METHODS: A sample of 471 alcohol-dependent subjects [363 European Americans (EAs) and 108 African Americans (AAs)] and 235 control subjects (192 EAs and 43 AAs) were included in the analyses. Alcohol dependence diagnoses were made using a structured interview. DNA isolated from whole blood was PCR-amplified, and genotypes were assigned on the basis of agarose gel size fractionation. RESULTS: Although allele frequencies differed significantly by population, there was no evidence of differences by diagnosis or as a function of any of the three subtypes. CONCLUSIONS: Variable findings in the literature in relation to the association of 5'-HTTLPR alleles to alcohol dependence seem to be due to factors other than the composition of study samples in terms of univariate typologies based on sex, comorbid drug dependence, or age of onset of alcohol dependence.
BACKGROUND: Association studies of a reportedly functional polymorphism in the promoter region (5'-HTTLPR) of the gene encoding the serotonin transporter protein (genetic locus SLC6A4) in alcoholics have yielded conflicting results. The most frequently observed alleles of the 5'-HTTLPR polymorphism are the short and long variants; the short variant is associated with lower transcriptional activity of the SLC6A4 gene than is the long variant. To reduce the heterogeneity that may confound association studies of alcohol dependence, we examined the association of 5'-HTTLPR alleles with three dichotomous typologies of alcoholism based on sex, comorbid drug dependence, or age of onset of alcohol dependence. METHODS: A sample of 471 alcohol-dependent subjects [363 European Americans (EAs) and 108 African Americans (AAs)] and 235 control subjects (192 EAs and 43 AAs) were included in the analyses. Alcohol dependence diagnoses were made using a structured interview. DNA isolated from whole blood was PCR-amplified, and genotypes were assigned on the basis of agarose gel size fractionation. RESULTS: Although allele frequencies differed significantly by population, there was no evidence of differences by diagnosis or as a function of any of the three subtypes. CONCLUSIONS: Variable findings in the literature in relation to the association of 5'-HTTLPR alleles to alcohol dependence seem to be due to factors other than the composition of study samples in terms of univariate typologies based on sex, comorbid drug dependence, or age of onset of alcohol dependence.
Authors: Martin A Javors; Chamindi Seneviratne; John D Roache; Nassima Ait-Daoud; Susan E Bergeson; M Consuelo Walss-Bass; Fatema Z Akhtar; Bankole A Johnson Journal: Prog Neuropsychopharmacol Biol Psychiatry Date: 2004-11-04 Impact factor: 5.067
Authors: Ana M D Carneiro; David C Airey; Brent Thompson; Chong-Bin Zhu; Lu Lu; Elissa J Chesler; Keith M Erikson; Randy D Blakely Journal: Proc Natl Acad Sci U S A Date: 2009-01-28 Impact factor: 11.205
Authors: Amira Pierucci-Lagha; Richard Feinn; Vania Modesto-Lowe; Robert Swift; Maggie Nellissery; Jonathan Covault; Henry R Kranzler Journal: Psychopharmacology (Berl) Date: 2003-09-10 Impact factor: 4.530