Local allele frequencies of the 5-HTTLPR serotonin transporter promoter polymorphism

Abstract

The Serotonin Transporter protein (5-Hydroxytryptamine transporter; 5-HTT) is an important reuptake receptor of serotonin from the synaptic cleft. The protein is encoded by the SLC6A4 gene. A size polymorphism, the 5-HTT Linked Polymorphic Region (5-HTTLPR; SLC6A4, 44-BP INS/DEL), exists within the promoter of this gene. The presence of this polymorphism has been associated with an increased susceptibility for a variety of neurological conditions including Parkinson disease, chronic pain, anxiety and depression related phenotypes. This 5' regulatory promoter polymorphism consists of a 44鈥揵ase pair insertion resulting in a long or short allele. The short allele is linked to a pronounced reduction in transcriptional efficiency producing lower numbers of transporter protein and a reduced rate of serotonin reuptake. Allele frequencies for this polymorphism show substantial variation in different populations. The frequency of the 5-HTTLPR in the population of Malta was determined in 608 cord blood DNA samples. Allele size difference of the 5-HTTLPR was detected using Polymerase Chain Reaction (PCR) and agarose gel electrophoresis. In total, 288 samples were found to be heterozygous (L/S) carrying 1 copy of the short allele and 1 copy of the long allele, while 129 samples were homozygous for the short allele (S/S) and 189 samples were homozygous for the long allele (L/L). Unexpectedly, 2 samples were found to carry a copy of the extra-long allele (XL) which is reportedly only found in African and Asian populations. Allele frequencies for L, S and XL alleles were 54.86%, 44.98% and 0.16% respectively. These local frequencies are similar to those of other European populations with the exception of the occurrence of the XL allele. These findings highlight the changing dynamics of population gene pools, the importance of selecting suitably matched controls for case-control studies and the importance of ethnicity information in the design, execution and interpretation of genetic diagnostic tests.