Alleles of a functional serotonin transporter promoter polymorphism are associated with major depression in alcoholics.
BACKGROUND
Serotonergic neurotransmission has been implicated in the pathogenesis of both alcohol dependence and mood disorders and may therefore be important in understanding the pathophysiology of comorbid alcohol dependence and major depression. Studies of the association of these disorders with a functional polymorphism in the promoter region of the gene encoding the serotonin transporter protein (locus SLC6A4) have yielded inconsistent results. Because the convergence of these disorders may provide a refined phenotype, we examined the association of serotonin (5-HT) transporter linked polymorphic region (5-HTTLPR) alleles to comorbid alcohol dependence and major depression.


METHODS
A sample of 296 European American and 16 African American patients with comorbid alcohol dependence and major depression was recruited from treatment studies. The control group included 260 European Americans and 43 African Americans; all were screened to exclude the presence of a mood or substance use disorder. DNA isolated from whole blood was polymerase chain reaction-amplified, and genotypes were assigned on the basis of agarose gel size fractionation.


RESULTS
The frequency of the short allele in the patient group was in the range of those previously reported for samples with unipolar depression but was significantly more common than among controls (short allele frequency of cases, 45.8%; controls, 39.8%; chi(2)(1) = 4.02; p = 0.045).


CONCLUSIONS
With respect to the frequency of the short allele at the SLC6A4 locus (5-HTTLPR), major depression in alcoholics is similar to major depression in nonalcoholics. Further efforts to characterize depressed alcoholics and to examine genetic predictors of response to antidepressant treatment seem warranted.
D000328:Adult; D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics* / Q000534:rehabilitation; D000483:Alleles; D044383:Black People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000453:epidemiology / Q000235:genetics* / Q000534:rehabilitation; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins; D044465:White People / Q000235:genetics; D001741:Black or African American
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins