DRD2基因多态性与美沙酮维持治疗剂量的关联性研究

Association between DRD2 gene polymorphisms and the dosage used on methadone maintenance treatment program

目的探讨DRD2基因的3个单核苷酸多态性位点（rs1800497、rs6275以及rs1799978）与美沙酮维持治疗剂量之间的关联。方法采用病例对照研究的方法，使用Quanto软件估算样本量至少180人。实际共纳入美沙酮维持治疗者257人，其中低剂量对照组89人，高剂量病例组168人。收集研究对象的一般情况、既往吸毒状况以及服药状况等信息，并对其进行DRD2基因分型，以探讨DRD2基因的多态性与美沙酮维持治疗剂量的关联性。结果DRD2基因rs6275位点基因型在不同美沙酮维持治疗剂量组间的分布差异有统计学意义，TC基因携带者相比于TT基因携带者（OR=0．338，95％CI：0．115～0．986），TC＋CC基因型携带者相比于TT基因型携带者（OR=0．352，95％CI：0．127—0．975）可能需要更低的美沙酮维持治疗剂量。尚未发现rs6275位点的等位基因，rs1800497位点、rs1799978位点的等位基因以及各遗传模型下的基因型在不同美沙酮治疗剂量组间分布的差异有统计学意义。结论DRD2基因rs6275位点与美沙酮维持治疗剂量有关联。尚未发现rs1800497位点、rs1799978位点与美沙酮维持治疗剂量有关联。

Objective To investigate the association between three single nucleotide polymorphism （SNP） genes DRD2 （rs1800497, rs6275, and rs1799978） and the dosage used on methadone maintenance treatment （MMT）. Methods From the methadone maintenance treatment centers, 257 MMT patients were recruited to participate in a case-control study and divided into two groups--control groups under low dosage （n= 89） and case （n= 168） group with high dosage. Quanto software was used to estimate the sample size as 180. Information related to social- demographic status, history on drug use and medication were collected. And DRD2 SNPs were genotyped to explore the relationship between polymorphism of DRD2 gene and the dosage of methadone maintenance treatment. Results Distributions of DRD2 rs6275 between different groups were significantly different. Patients carrying TC genotype needed lower dose of methadone when compared to the patients that carrying CC genotype counterparts （0R=0.338, 95% CI： 0.115-0.986）. Patients that carrying C allele at rs6275 needed lower methadone dose than those that carrying genotype TT （OR= 0.352, 95% CI： 0.127-0.975）. Distributions of genotypes, alles in the other two SNPs （rs1800497, rs1799978） were not significantly different between groups under different dosages. Conclusion DRD2 rs6275 was associated with dosage of methadone used for the MMT patients. However, no significant associations were found between rs 1800497, rs 1799978 and the dosage of methadone.