GENETIC BASIS OF ALCOHOL DEPENDENCE: TRIALLELIC POLYMORPHISM OF THE SEROTONIN TRANSPORTER GENE IN A POPULATION OF ALCOHOL DEPENDENT SUBJECTS FROM ITALY

Background: The involvement of genetic variants in the neurobiology of addiction and in the pathways of reward circuits is well established. Serotonin transporter (5-HTT) regulate serotonergic neurotransmission and has been associated also with alcohol dependence (AD). Aim of this study is to assess a possible link between a tri-allelic polymorphism of the 5’-UTR region of 5-HTT gene (SLC6A4) and AD. This tri-allelic polymorphism is made up of the long (L) allele of 5-HTTLPR polymorphism together with the A (La) or G (Lg) allele of the rs25531 single nucleotide polymorphism (SNP) and the short allele (S). Lg and S are the low-functioning alleles. Methods: Genotyping was performed by PCR amplification of the 5-HTTLPR region; this produces long (L) or short (S) amplicons depending on the variable number of repeated elements, that results, in most cases, in a 43 base pair insertion/deletion. The rs25531 genotype was obtained by an L specific PCR amplification followed by a mini sequencing reaction. We investigated 439 Italian alcoholic outpatients (male 350, female 89) at Alcohol Unit of Umberto I Hospital - Sapienza University of Rome and 423 healthy controls (male 285, female 138). Results: From allelic point of view, no statistically significant difference could be evidenced between alcoholics and controls, considering either overall population or males separated from females. However, AD women showed higher frequency of both the L (56.2%) and La (51.7%) allele than control women (respectively 50.4% and 47.5%), although not statistically significant probably because of the smallness of the sample analysed. An higher frequency of the L allele statistically significant (P <0.05), can be only observed in women with an early first contact with alcohol (≤16 yo, 63.5%) compared to control (50.4%). Conclusions. According to our results, the 5HTTLPR and rs25531 polymorphisms of the serotonin transporter gene (SLC6A4) seems not to be generally involved in AD. However, considering males and females together can lead to underestimate important differences in allelic distribution. In fact, at least some categories of female patients show an higher percentage of “fully working” alleles (L and La). Genotypic analysis and studies of larger populations are mandatory.