OBJECTIVE The N-methyl-D-aspartate receptor is consisting of three subfamilies (NR1, NR2A,2B, 2C, 2Dand NR3A, 3B).The ability of NR3A to modulate the NMDAR function makes it an attractive candidate gene of heroin addiction.The purpose of this study is to explore the association between two single nucleotide polymorphisms (SNPs) (rs3739722, rs17189632) in the glutamate receptor subunit gene (GRIN3A) and heroin addiction.METHODS The genotypes of the two SNPs (rs3739722, rs17189632) in 332 heroin dependent patients and 200 normal control subjects in the male Han Chinese population were detected by TaqMan SNP genotyping method, and the association between heroin dependence and the two SNPs was analyzed.RESULTS The distributions of genotype and allele at rs3739722 were not significantly different between in the cases and in the control group (P>0.05).The frequencies of genotype and allele at rs17189632 were significantly different between the cases and the controls (x2 =7.237, P=0.0268; x2 =4.278, P=0.0386).In addition, the A allele frequency of rs17189632 was significantly lower in cases compared with the control group (OR=0.752, 95% Cl 0.574-0.986, P=0.0386).And the frequency of AA genotype of rs17189632 was significantly lower in cases compared with the control group (OR=0.457, 95% Cl 0.255-0.818, P=0.0073).CONCLUSION Our study indicates that the rs17189632 of the glutamate receptor subunit gene (GRIN3A) play a major role in heroin dependence.