The major alleles within this VNTR differ in the number of copies of a 20- to 23-bp imperfect repeated sequence. The L allele, which leads to increased transcriptional efficiency, has 16 copies of the repeat and the S allele has 14 copies.85 Further, there is a relatively common, functional A > G single-nucleotide polymorphism (SNP) within the L allele,86 the LG allele being equivalent to the S allele in transcriptional efficiency.86 Further supporting the functional effect of HTTLPR, this locus has been shown to regulate serotonin transporter expression in postmortem brain87 and in vivo using single-photon emission computed tomography (SPECT) imaging88 although not in all studies.89 Low-transcribing HTTLPR genotypes have been inconsistently associated with anxiety, depression, and alcoholism. However, the effects of this locus on complex behavior appear stronger if environmental exposure is also considered. HTTLPR moderated the impact of stressful life events on risk of depression and suicidal behavior.90 Carriers of the low-transcribing S allele exhibited more depression and suicidality after stressful life events than L individuals with two copies of the allele.90 Although a meta-analysis failed to support
