Tyrosine Hydroxylase Gene Polymorphisms Contribute to Opioid Dependence and Addiction by Affecting Promoter Region Function.

Abstract

Mounting evidence shows that drug dependence involves the complex interplay betweengeneticsand the environment. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine (DA) synthesis, which plays an essential role in the development of drug addiction. Noradrenergic dysfunction due to abnormalities TH expressionhas been implicated in the pathogenesis of drug addiction. We profiled thirteensingle-nucleotide polymorphisms (SNPs) and one VNTR (TCATrepeat, UniSTS:240,639) in 512 cases and 600 healthy Chinese subjects to evaluate the relationship between common variants within the TH gene and opioids dependence (OD) in the Chinese Han population. The single-marker analysis determined that rs10770141 (p < 0.001, OR 1.739, 95% CI 1.302 - 2.323) and rs10770140 (p = 0.002, OR 1.536, 95% CI 1.164 - 2.026) are risk variants for OD. The haplotype-association analyses determined that A-C-C-C was a risk factor (p = 0.006, OR 1.662, 95% CI 1.241 - 2.225) for OD. We also observed a significant association between (TACT)9/9 and the duration of transition from the first time using opioids to the development of opioid dependence (DTFUD) (p = 0.002, OR 2.153, 95% CI 1.319 - 3.513). Taken together, this study suggests that TH gene polymorphisms may contribute to the risk of OD in the Chinese Han population.