<b><i>TPH1</i></b> and <b><i>5-HTTLPR</i></b> Genes Specifically Interact in Opiate Dependence but Not in Alcohol Dependence

Abstract

Background: Different drug dependencies may have unique genetic vulnerabilities. Changes in serotonin availability and function have been linked to addiction. We investigated whether 2 serotonergic polymorphisms, TPH1 A218C (rs1800532) and 5-HTT-linked promoter region (5-HTTLPR) (rs25531), are differently associated with alcohol or opiate dependence. Methods: Alcohol-dependent patients (n = 292), opiate-dependent patients (n = 309), and healthy controls (n = 301) were recruited from the Han Chinese population in Taiwan. Genotypes of TPH1 A218C and 5-HTTLPR polymorphisms were analyzed using a polymerase chain reaction with restriction fragment length polymorphism. Results: The genotype frequencies of the TPH1 A218C polymorphisms were not significantly different in the 3 groups. The genotype frequencies of the 5-HTTLPR S+ (S/S, S/L_G, L_G/L_G) polymorphisms were significantly higher in opiate-dependent patients (χ² = 8.77, p = 0.01), but not after controlling for the covariates of age, gender, and interaction effect in logistic regression analysis. Moreover, there was a significant interaction between the TPH1 A218C A/C and 5-HTTLPR S+ gene polymorphisms in opiate-dependent (OR 2.72, p = 0.01), but not in alcohol-dependent patients. Conclusions: Our data suggested that there may be a differential genetic vulnerability in serotonergic genes for alcohol and opiate addiction. However, replications of our findings are still needed.

Association between serotonin transporter gene polymorphisms and heroin dependence: a meta-analytic study

“…Although heterogeneity test of the included studies did not show significant difference in their effect sizes, ethnic difference may cause a differential distribution of genetic polymorphisms, evidenced by a significant increase in the L allele in the controls of three studies with Caucasian subjects21,28,29 than that in the others25,27,32 (56.8% vs 38.6%, P <0.001). So, the association of the 5-httlpr polymorphism with HD was also examined separately in studies with Caucasian and non-Caucasian subjects.…”

“…Six studies, with 2,459 subjects (868 patients and 1,591 controls), were included into the analysis (Table 1). While only two studies showed a significant association of the S allele with HD, 21,32 other studies showed no association (Figure 1A). The homogeneity analysis showed a negative result ( χ 2 =4.72, df =5, P =0.451), which suggested that the effect sizes from individual studies were not statistically different and justified the use of fixed effects model.…”

“…21,32 Expression of serotonin transporter protein was influenced by the 5-httlpr , where the L allele produced the expression level much higher than the S allele 12,13. Moreover, 5-HTT binding sites and mRNA levels in the dorsal raphe, median raphe, and the substantia nigra of postmortem brains also varied by 5-httlpr genotypes, with the highest levels from subjects with LL genotype rather than LS or SS genotype 34.…”