Allelic association analysis of dopamine D2, D3, 5-HT2A and GABAg2 receptors and the serotonin transporter genes with heorin abuse in chinese subjects

Abstract

Five candidate genes, the receptors DRD2, DRD3, HTR2A and GABAg2, and the serotonin transporter (5-HTT) were examined for association analysis with heroin abuse. We examined three polymorphisms (promoter -141DC, Ser311Cys, and 'Taq I') in the DRD2, one polymorphism (Ser9Gly) in DRD3, two polymorphisms (promoter -1438G/A and T102C) in HTR2A, two polymorphisms (VNTR and Del/Ins) in 5-HTT gene, and one polymorphism (G3145A) in GABAg2 gene in 121 Chinese heroin addicts and 180 controls. All polymorphisms did not differ significantly for allele, genotype, or haplotype frequencies, except for DRD2 promoter polymorphism (genotype-wise and allele-wise, P = 0.05). An additional 344 subjects with heroin abuse and 118 control were investigated for DRD2 promoter polymorphism. There were no significant difference of genotype or allele frequencies between subjects with heroin abuse and normal controls. However when we divided the sample by route of administration into nasal inhalers and IM or IV injectors, it produced a significant difference between inhaler of heroin and controls (genotype-wise, P=0.006, allele-wise, P=0.016) but not for injectors of heroin (genotype-wise, P=0.81, allelewise, P=0.69). Overall our results indicates that the HTR2A, 5-HTT, DRD3 and GABAg2 genes are not likely to be a major genetic risk factor for heroin abuse in this population, with the exception of possible association between nasal inhalation and DRD2 promoter -141DC polymorphism.