Serotonin transporter promoter polymorphism in African Americans : allele frequencies and implications for treatment.
BACKGROUND
Americans of African ancestry are less likely to receive a selective serotonin reuptake inhibitor (SSRI) for treatment of major depressive disorder than Americans of European ancestry. A functional insertion/deletion polymorphism in the promoter of the serotonin transporter (5-HTT) gene SLC6A4 has been shown to modulate SLC6A4 transcription, affecting response to SSRIs. Several studies in populations of predominantly European ancestry have consistently found that the SLC6A4 promoter polymorphism (referred to as the 5-HTT-linked polymorphic region; 5-HTTLPR) long (L) allele is associated with better response to SSRI treatment than the short (S) allele.


OBJECTIVE
The frequency of SLC6A4 (5-HTTLPR) alleles in 865 black Americans and Afro-Caribbeans was examined to assess possible implications for treatment.


METHODS
SLC6A4 (5-HTTLPR) genotypes were determined in individuals with self-identified African ancestry from South Carolina (n = 489), western Pennsylvania (n = 207), and Tobago (n = 169). Frequencies were compared using chi-square analyses.


RESULTS
It was verified that the L allele is highly prevalent in Americans of African ancestry, ranging from 77% in western Pennsylvania to 87% in South Carolina. The frequency of the SLC6A4-(L) allele is significantly higher in African-Americans than has been reported for European-Americans (typically 56-60%). There are both statistically significant geographic differences and slight deviations from Hardy-Weinberg equilibrium.


CONCLUSIONS
Given the potential influence on treatment response, these findings have implications for the use of SSRIs in this population. The results suggest that additional studies to examine the impact of these alleles on treatment response in African-Americans are warranted.
Department of Psychiatry, Western Psychiatric Institute and Clinics, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA. lotrichfe@msx.upmc.edu
Francis E
FE
Lotrich
Bruce G
BG
Pollock
Robert E
RE
Ferrell
D001741:Black or African American / Q000706:statistics & numerical data*; D002352:Carrier Proteins / Q000235:genetics*; D016009:Chi-Square Distribution; D005787:Gene Frequency / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010414:Pennsylvania; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins; D013022:South Carolina; D014300:Trinidad and Tobago
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins