Serotonin Transporter Promoter Polymorphism in African Americans
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ORIGINAL RESEARCH ARTICLE
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Serotonin Transporter Promoter Polymorphism in African Americans Allele Frequencies and Implications for Treatment Francis E. Lotrich,1 Bruce G. Pollock1 and Robert E. Ferrell2 1 2
Department of Psychiatry, Western Psychiatric Institute and Clinics, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Abstract
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. Study design and 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.
Major depression is a common disorder. Recent surveys indicate a 1-year prevalence in the adult population of between 5% and 10%.[1] However, little is known about the effect of ethnicity on response to antidepressant treatment. Despite this, studies report disparity in treatments offered to black American patients compared with patients of European ancestry.[1] Not only are black Americans less likely to be diagnosed with depression, but once diagnosed they are prescribed antidepressants less often, particularly selective serotonin reuptake inhibitors (SSRIs).[2,3] The serotonin transporter (5-HTT) is encoded by the SLC6A4 gene. The promoter region contains a functional insertion/deletion
polymorphism with two common
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