Functional polymorphisms of the glutamate receptor N-methyl D-aspartate 2A gene are associated with heroin addiction

Abstract

ABSTRACT. Heroin dependence is a debilitating psychiatric disorder with a complex inheritance mechanism. Genetic polymorphisms in functional regions of the glutamate receptor, N-methyl D-aspartate 2A (GRIN2A) gene, which encodes the 2A subunit of the N-methyl D-aspartate (NMDA) receptor, may modulate the risk of heroin addiction. We investigated the potential association between 8 single nucleotide polymorphisms (SNPs) of the GRIN2A gene (SNPs rs3219790, rs1014531, rs8044472, rs8045712, rs9933624, rs9940680, rs1420040, and rs767749) and heroin addiction using the MassARRAY system and GeneScan. A total of 405 heroin-addicted patients and 397 healthy control subjects were recruited for this study. Statistically significant differences were observed for rs3219790 in the promoter region of the GRIN2A gene. The frequency of the (GT)26 repeats in the heroin addiction group was significantly higher than that in the control group [c 2 = 5.475, P = 0.019, odds ratio (OR) = 1.367, 95% confidence 8715©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 13 (4): 8714-8721 (2014) Polymorphisms of GRIN2A in heroin addiction interval (CI) = 1.051-1.776]. Strong linkage disequilibrium was observed in block 1 (D' > 0.9). However, significant evidence of linkage disequilibrium was not observed between the 7 SNPs in our sample population. These data suggest that GRIN2A gene polymorphisms confer susceptibility to heroin addiction and support the hypothesis that dysfunction of GRIN2A is involved in the pathophysiological process of heroin addiction.

Glutamatergic and GABAergic susceptibility loci for heroin and cocaine addiction in subjects of African and European ancestry

“…GRIN2A SNP rs1650420 that was indicated in this study in association with OD in AA by the less stringent cutoff ( P = 0.019), was previously associated with OD in Han Chinese (Zhao et al, 2013; Zhong et al, 2014) and in our previous study of in AA (Levran et al, 2009). …”

“…We have reported an association of GRIN2A SNPs with heroin addiction (opioid dependence/OD) in a subsample of the current sample of African Americans (AA) (Levran et al, 2009). GRIN2A SNPs were also associated with OD in Han Chinese (Zhao et al, 2013; Zhong et al, 2014). GABRA2, GABRB3, GABRG2, and GAD1 SNPs were associated with OD in different populations (Loh et al, 2007; Enoch et al, 2010; Wu et al, 2012; Chen et al, 2014; Li et al, 2014; Yang et al, 2014).…”

An Association Study on the Glutamate Pathway GRIN2A Gene Polymorphisms with Heroin Dependence

“…Another study on Han Chinese population also identified association of GRIN2A polymorphisms and haplotypes with heroin addiction [5]. Studies also showed association of GRIN2A GT repeat polymorphism with alcohol and heroin addiction patients [14,16], supporting the hypothesis of GRIN2A dysfunction in the pathophysiology of heroin dependence [16].…”

“…Single nucleotide polymorphisms in GRIN2A, have been extensively studied in recent years and results have revealed them to be possibly associated with drug addiction, including alcohol and heroin [13][14][15][16]. A variable GTn repeat in the 5'-regulatory region of N-methyl-Daspartate GRIN2A subtype was identified and significantly associated with alcohol dependence [14,23].…”

“…The GRIN2A gene is located on chromosome 16p13.2 with twelve exons. Various studies investigated polymorphisms of the GRIN2A gene and suggested their association with heroin and alcohol addiction [13][14][15][16]. In a study on African-American population, GRIN2A was identified as the most potential candidate gene after screening 130 genes involved in heroin addiction [13].…”