Association Study of Genetic Polymorphisms in GABRD with Treatment Response and Dose in Methadone Maintenance Treatment

Abstract

Aim: This study determined if gene variants in the GABA receptor delta subunit (GABRD) are associated with treatment response and dose in methadone maintenance treatment (MMT) for heroin addiction. Materials & methods: A total of 286 MMT patients were recruited and divided into response and nonresponse groups based on retention time in therapy. A total of 177 responders were classified into low dose and high dose subgroups according to the stabilized methadone dose. Four (single nucleotide polymorphisms) SNPs (rs13303344, rs4481796, rs2376805 and rs2229110) in GABRD were genotyped using the TaqMan SNP assay. Logistic regression was used to assess the genetic effects of the SNPs in MMT. Results: No significant associations were observed between the SNPs and treatment response or dose, except the frequency of haplotype ACGC at the four SNPs significantly differed between responders and nonresponders. Conclusion: The results indicated that GABRD variants may play a small role in modulating methadone treatment response.

Lay abstract

This study determined if gene variants in the GABA receptor delta subunit (GABRD) are associated with treatment response and dose in methadone maintenance treatment (MMT) for heroin addiction. A total of 286 MMT patients were recruited and divided into response and nonresponse groups. A total of 177 responders were classified into low and high dose subgroups. Four single nucleotide polymorphisms (SNPs) (rs13303344, rs4481796, rs2376805 and rs2229110) in GABRD were genotyped and assessed the genetic effects of the SNPs in MMT. No significant associations were observed between the SNPs and treatment response or dose, except the frequency of haplotype ACGC significantly differed between responders and nonresponders. The results indicated that GABRD variants may play a small role in MMT, which may help provide a foundation for personalized solutions for MMT.

Keywords::

• association
• GABA receptor
• gene polymorphism
• heroin
• methadone

Acknowledgments

The authors express their gratitude for the contributions of all participants in the study.

Financial & competing interests disclosure

This study was supported by the National Natural Science Foundation of China (number 81671321, 82071499); the Medical Health Science and Technology Projects of Zhejiang, China (number 2021KY1065); and the Science and Technology Program of Ningbo, China (number 2019A610296). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The study was approved by the ethical committee of Ningbo Addiction Research and Treatment Center (Zhejiang Province, China). Informed consent was obtained from participants in the study.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (number 81671321, 82071499); the Medical Health Science and Technology Projects of Zhejiang, China (number 2021KY1065); and the Science and Technology Program of Ningbo, China (number 2019A610296). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.