Analysis of variations in the glutamate receptor, N-methyl D-aspartate 2A (GRIN2A) gene reveals their relative importance as genetic susceptibility factors for heroin addiction.
The glutamate receptor, N-methyl D-aspartate 2A (GRIN2A) gene that encodes the 2A subunit of the N-methyl D-aspartate (NMDA) receptor was recently shown to be involved in the development of opiate addiction. Genetic polymorphisms in GRIN2A have a plausible role in modulating the risk of heroin addiction. An association of GRIN2A single-nucleotide polymorphisms (SNPs) with heroin addiction was found earlier in African Americans. To identify markers that contribute to the genetic susceptibility to heroin addiction, we examined the potential association between heroin addiction and forty polymorphisms of the GRIN2A gene using the MassARRAY system and GeneScan in this study. The frequency of the (GT)26 repeats (rs3219790) in the heroin addiction group was significantly higher than that in the control group (χ(2) = 5.360, P = 0.021). The allele frequencies of three polymorphisms (rs1102972, rs1650420, and rs3104703 in intron 3) were strongly associated with heroin addiction (P<0.001, 0.0002, and <0.001, after Bonferroni correction). Three additional SNPs from the same intron (rs1071502, rs6497730, and rs1070487) had nominally significant P values for association (P<0.05), but did not pass the threshold value. Haplotype analysis revealed that the G-C-T-C-C-T-A (block 6) and T-T (block 10) haplotypes of the GRIN2A gene displayed a protective effect (P = <0.001 and 0.003). These findings point to a role for GRIN2A polymorphisms in heroin addiction among the Han Chinese from Shaanxi province, and may be informative for future genetic or neurobiological studies on heroin addiction.
College of Forensic Science, Xi'an Jiaotong University, Key Laboratory of Ministry of Public Health for Forensic Science, Xi'an, Shaanxi, PR China.
Bin
B
Zhao
Yongsheng
Y
Zhu
Wei
W
Wang
Hai-Min
HM
Cui
Yun-Peng
YP
Wang
Jiang-Hua
JH
Lai
D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006556:Heroin Dependence / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA
D016194:Receptors, N-Methyl-D-Aspartate