Pharmacogenetic Approach to Treating Drug Dependence: Serotonin Transporter Gene (SLC6A4) Promoter Polymorphisms as Treatment Predictors in Jordanian Arabs

Laith   N.   AL-Eitan; Saied   A.   Jaradat; Gary   K.   Hulse; Guan   K.   Tay

doi:10.2174/187569212803901783

Abstract

Alterations in serotonin availability, levels and function have been shown to affect drug consumption patterns, behavior and responses to treatment. Despite the existence of health burdens related to drug dependence in resourcelimited settings outside the realm of developed countries, there have been relatively few public health pharmacogenetics studies focusing on drug dependence in developing countries outside Europe and North America. This study examines the influence of SLC6A4 gene polymorphisms (5-HTTLPR and rs25531) on clinical and biological outcomes of drug dependence in patients of Arab descent in a sample from Jordan. PCR-RFLP based genotyping of the 5-HTTLPR gene variants (LL/LS/SS) and rs25531 marker polymorphisms (A/G) was performed in 192 drug dependent patients of Arab descent. These patients were undergoing an 8-week pharmacological and behavioral inpatient treatment program. In treatment, end of treatment and follow-up outcome measures included changes in drug consumption and alcohol intake, urine drug screen, alcohol breath test, days in treatment, counselling and self-help group sessions and completion rate. Patients were stratified according to receptor polymorphism using a bi-allelic (Group A: LL versus Group B: SS and LS genotype) and a tri-allelic approach (Group A’: LA/LA versus Group B’: non-LA/LA genotype). Bonferroni corrections were applied for multiple comparisons. There were no significant differences between genotype subgroups regarding severity of drug dependence, psychiatric status, past history, medications (p> 0.1). However, the frequency of drug use, reduction in heroin consumption and alcohol intake and responsiveness to treatment were significantly different for the LL, LS and SS genotypes (p< 0.05). In addition, assuming a dominant effect of S(Group A versus Group B), a significant difference in the age of first drug use was observed (p< 0.05). Notably, patients with the LL genotype were younger when they first used drugs. Group A’ compared to Group B’ showed a significant difference in age of first use, drug use frequency and detoxification with higher averages in patients who were carrying the LA allele (p < 0.05). To the best of our knowledge, this is the first study of serotonin transporter polymorphisms (5-HTTLPR and rs25531) and the clinical and biological outcomes of drug dependence in patients of Arab origin. We conclude with a discussion of these findings with a view to the emerging nascent field of “public health pharmacogenetics”, and personalized medicine diagnostics for rational treatment of drug dependence as seen through the lens of global postgenomics science.

Keywords: Global personalized medicine, Jordan, opiate drug dependence, public health pharmacogenetics, SLC6A4, treatment response.

« Previous Next »