AUTHOR=Wang Li , Bai Mei , Jin Tianbo , Zheng Jianwen , Wang Yuhe , He Yongjun , Yuan Dongya , He Xue 

TITLE=Effects of CYP3A4 Polymorphisms on Drug Addiction Risk Among the Chinese Han Population

JOURNAL=Frontiers in Public Health

VOLUME=7

YEAR=2019

URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2019.00315

DOI=10.3389/fpubh.2019.00315

ISSN=2296-2565

ABSTRACT=<p><bold>Background:</bold><italic>Cytochrome P450 3A4</italic> (<italic>CYP3A4</italic>) regulates pharmacokinetic and pharmacodynamic interactions during the process of drug absorption and metabolism, suggesting <italic>CYP3A4</italic> plays an important role in drug addiction. However, the association between <italic>CYP3A4</italic> polymorphisms and drug addiction risk is still not clear.</p><p><bold>Methods:</bold> This case-control study included 504 drug addicts and 501 healthy controls from Xi'an, China. Four single nucleotide polymorphisms (SNP) in <italic>CYP3A4</italic> (rs3735451, rs4646440, rs35564277, and rs4646437) were genotyped by Agena MassARRAY platform. After adjusting by age and gender, we calculated odd ratios (OR) and 95% confidence intervals (CI) by logistic regression to estimate the association between <italic>CYP3A4</italic> polymorphisms and drug addiction risk.</p><p><bold>Results:</bold> We found rs4646440 and rs4646437 were associated with decreased risk of drug addiction in codominant (rs4646440: <italic>OR</italic> = 0.41, 95%CI = 0.19–0.92, <italic>p</italic> = 0.030; rs4646437: <italic>OR</italic> = 0.19, 95%CI = 0.04–0.87, <italic>p</italic> = 0.032) and recessive (rs4646440: <italic>OR</italic> = 0.41, 95%CI = 0.19–0.91, <italic>p</italic> = 0.028; rs4646437: <italic>OR</italic> = 0.20, 95%CI = 0.04–0.90, <italic>p</italic> = 0.036) models. Rs3735451 and rs4646437 were associated with drug addiction risk in the subgroup of middle-aged people (44 &lt; age ≤ 59) and elderly people (age ≥ 60), individually. For men, rs3735451, rs4646440, and rs4646437 had strong relationship with decreased risk of drug addiction (<italic>p</italic> &lt; 0.05). The effects of rs3735451 on drug addiction risk were related to drug-using time (<italic>p</italic> &lt; 0.05). We also observed one block (rs4646440 and rs35564277) in haplotype analysis.</p><p><bold>Conclusion:</bold><italic>CYP3A4</italic> polymorphisms were associated with drug addiction risk among the Chinese Han population.</p>