Characterization of serotonin transporter gene ( SLC6A4 ) polymorphisms and its association with drug dependence in a Jordanian Arab population

Abstract

Drug dependence is a pattern of repeated self-administration of a drug, which can result in tolerance, withdrawal and compulsive drug-taking behaviour. It has been recently suggested that 5-HTTLPR (LL/LS/SS) variants and rs25531 (A/G) polymorphism in the serotonin transporter gene (SLC6A4) may play a role in drug dependence. The current study aimed to (1) identify allelic, haplotypic and genotypic frequencies of the 5-HTTLPR variants and rs25531 polymorphisms of SLC6A4 gene in drug and nondrug-dependent Jordanian Arab population and (2) determine whether there is an association of these variants in a drug-dependent population from the same area. Jordanian drug male addicts of Arab descent (n = 192) meeting the Diagnostic and Statistical Manual of Mental Disorders – Fourth edition criteria for drug dependence and 230 healthy male controls from an ethnically homogenous Jordanian Arab population were examined. Genotyping was performed using the restriction fragment length polymorphism–polymerase chain reaction-based method to genotype the 5-HTTLPR variants and detect the A/G polymorphism at position rs25531. The biallelic analysis revealed that the frequency of 5-HTTLPR (LL/LS/SS) genotypes was statistically significant different between drug-dependent individuals and controls (χ ² (2, N = 422), p = 0.04). Drug-dependent subjects had a higher frequency of ‘L’ allele. However, using the triallelic approach, the estimated frequency of haplotypes (S_A , S_G , L_A and L_G ) and phased genotypes (L_A /L_A , L_A /S_A , L_A /L_G , S_A /S_A and S_A /S_G) did not show significant association with drug dependence (χ ² (3, N = 422), p = 0.53 and χ ² (4, N = 422), p = 0.06, respectively). This study suggests a putative role of the 5-HTTLPR for drug dependence in the Jordanian Nationals of Arab ancestry.