Dipendenza da eroina e lunghezza dei telomeri nei leucociti

Telomeres are repetitive sequences at the end of chromosomes that play a key role in the maintenance of genomic stability. In general, during each cellular division, the telomeres shorten but also other external factor, like various mental states, depressed mood, drug and alcohol addiction can lead to an accelerated erosion of the chromosome terminal portion. To this end, the present study sought to investigate the correlation between heroin abuse and leukocyte telomere length (LTL). For a subgroup of heroin-dependent patients and healthy controls, we also analysed the association between LTL and the 5-HTTLPR polymorphism. The 5-HTTLPR polymorphism is a 44 bp insert / deletion located in the promoter region of the gene encoding for the serotonin transporter (hSERT). The short variant (S\S) is associated with a lower expression of 5-HTT and, as recently shown in a Chinese population, with shorter LTL. The study was conducted on a sample of 99 heroin-dependent patients, in methadone maintenance therapy, and 99 healthy controls. The patients were diagnosed by the Drug Addiction Service in Cagliari (ASL8), according to the criteria of DSM-IV. The genomic DNA extraction was performed by conventional salting-out method and the relative quantification for LTL was carried out with qPCR by SYBR Green Assay using Step One Plus Instrument (ThermoFisher). The LTL was calculated using the 2-ΔΔCT method (ΔΔCT = ΔCT sample - ΔCT calibrator; ΔCT sample = CT Tel gene - CT Hgb gene). The Polymerase Chain Reaction (PCR) was used to identify genotypes for the 5-HTTLPR polymorphism. The association between LTL and quantitative (e.g., age at sampling) and dichotomous variables (e.g., sex, diagnosis for heroin addiction) was evaluated using the Spearman correlation test and the U test of Mann- Whitney, respectively. To evaluate the association between LTL and clinical variables, correcting for age at sampling, a linear regression model was constructed using LTL as the dependent variable, clinical variables as predictors and age as covariate. Finally, the association between LTL and the 5-HTTLPR polymorphism genotype was also evaluated using a linear regression model with LTL as the dependent variable, the genotype as a predictor, and the age of withdrawal as a covariate. We found a negative correlation between LTL and age at sampling (Spearman rho = -0.17, p = 0.015) and no association with sex. The Mann Whitney's U test did not highlight a difference in mean LTL between heroin-dependent patients and healthy controls. No clinical variable analysed was associated with LTL. Finally, the linear regression model did not reveal a significant association between LTL and the genotype for 5-HTTLPR polymorphism . Our study didn’t show a significant correlation between LTL, heroin addiction and the genotype for 5-HTTLPR polymorphism. This finding does not support the hypothesis of heroin addiction as an illness associated with accelerated telomere shortening. However, more studies on larger independent samples controlling for potential variables suggested to be able to exert an impact on LTL are necessary.