Serotonin transporter promoter polymorphism in African Americans : allele frequencies and implications for treatment.
Serotonin transporter promoter polymorphism in African Americans : allele frequencies and implications for treatment.
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DOI：
10.2165/00129785-200303020-00007
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发表时间：
2003-01-01
期刊：
影响因子：
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通讯作者：
Ferrell, Robert E
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文献类型：
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作者：
Lotrich, Francis E;Pollock, Bruce G;Ferrell, Robert E
背景：非洲裔美国人接受选择性血清素再摄取抑制剂（SSRI）治疗重度抑郁症的可能性低于欧洲裔美国人。5-羟色胺转运体（5-HTT）基因SLC6A4启动子的功能性插入/删除多态性已被证明可以调节SLC6A4的转录，影响对SSRIs的反应。在以欧洲血统为主的人群中进行的几项研究一致发现，SLC6A4启动子多态性（称为5- httlink多态性区域；5-HTTLPR）长(L)等位基因比短(S)等位基因对SSRI治疗的反应更好。目的：研究865名美国黑人和加勒比黑人SLC6A4 （5-HTTLPR）等位基因的频率，以评估可能对治疗的影响。研究设计和方法：在南卡罗来纳州（n = 489）、宾夕法尼亚州西部（n = 207）和多巴哥（n = 169）自认为非洲血统的个体中测定SLC6A4 （5-HTTLPR）基因型。使用卡方分析比较频率。结果：证实L等位基因在非洲裔美国人中非常普遍，从宾夕法尼亚州西部的77%到南卡罗来纳州的87%不等。SLC6A4-(L)等位基因在非洲裔美国人中的频率明显高于欧洲裔美国人（通常为56-60%）。统计上有显著的地理差异，也有轻微偏离Hardy-Weinberg均衡。结论：考虑到对治疗反应的潜在影响，这些发现对在该人群中使用SSRIs具有启示意义。结果表明，进一步研究这些等位基因对非裔美国人治疗反应的影响是有必要的。
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.