Association of the DRD4 exon III and 5-HTTLPR VNTR polymorphisms with substance abuse in Jordanian Arab population

Abstract

Genetic variations in the dopamine D4 receptor (DRD4) gene and the serotonin transporter (SLC6A4) gene are involved in the aetiology of substance abuse disorder (SUD). The main aim of this study is to evaluate the genetic association of DRD4 (48 bp-VNTR) and SLC6A4 (rs25531 and 5-HTTLPR VNTR) gene polymorphisms with SUD susceptibility among the Jordanian Arab population. This study included 500 SUD patients and 500 healthy matched controls. The VNTR Genetic polymorphisms of DRD4 and SLC6A4 genes were genotyped using conventional polymerase chain reaction (PCR). While, the rs25531 SNP was genotyped using PCR-restriction fragment length polymorphism (PCR-RFLP) technique. The genetic association was analysed using different statistical analyses including chi-square, Fisher exact test and one way ANOVA test. The DRD4 exon III VNTR polymorphism was associated with SUD significantly in case of alleles 4, 7 and genotype 7/7 (P = 0.004, 0.0005 and 0.01, respectively). While, there was no genetic association between the 5-HTTLPR (LL, LS, SS), rs25331 (AA, AG, GG) and tri-allelic (SASA, LASG, LASA, LALG, LALA) genotypes (P = 0.26, 0.71 and 0.52, respectively) and SUD. Moreover, using multinomial regression analysis, the homozygous 7/7 and 2/2 VNTR genotypes of DRD4 gene were nominally significantly associated with a lower risk of addiction (OR = 0.285 with P = 0.003 and OR = 0.447 with P = 0.031, respectively) after adjusting for other covariates. Our findings showed that 4 and 7 repeats and the genotype 7/7 of DRD4 exon III VNTRs polymorphism are involved in the aetiology of SUD among Jordanian population in compared to the 5-HTTLPR polymorphisms.