Preliminary evidence of ethnic divergence in associations of putative genetic variants for methamphetamine dependence

Abstract

Research into the biological processes that increase susceptibility to methamphetamine dependence has been conducted primarily in Asian populations. Using a case-control design this study's purpose was to explore, among a population of methamphetamine-dependent Caucasians, six putative single nucleotide polymorphisms previously found to be associated with methamphetamine dependence in Asian populations. 193 non-psychotic males (117 methamphetamine-dependent and 76 controls) were genotyped for variants located in six genes (AKT1, ARRB2, BDNF, COMT, GSTP1, OPRM1). Genotypic and allelic frequencies, odds ratios, and 95% confidence intervals were calculated. None of the putative gene associations were significantly replicated in our sample of Caucasian men. Effect size comparisons suggest a trend toward allelic divergence for arrestin beta 2 (ARRB2) and glutathione S-transferase P1 (GSTP1) and allelic convergence for brain-derived neurotrophic factor (BDNF). Results provide preliminary support for further exploration and validation of candidate SNPs for METH dependence reported among Asian populations across other ethnic/ancestral groups.

BDNF (Val66Met) Genetic Polymorphism is Associated with Vulnerability for Methamphetamine Dependence

“…Furthermore, Sim et al [14] reported a significant increase in the GG genotype in a small (n = 24) Chinese subgroup of Malaysian METH-dependent subjects, which was not found in other Malaysian ethnic groups. However, METH dependence in a male Caucasian sample showed no association with this polymorphism [16].…”

“…This too is consistent with the finding from Sim et al [14], and may also provide an explanation for the lack of association between rs6265 and METH abuse in the Japanese sample studied by Itoh et al [15] as the latter group studied solely METH-dependent subjects who were diagnosed as having a psychotic disorder. The fact that the samples of Bousman et al [16] were all nonpsychotic subjects indicates that the observed association, consistent in Chinese and Thai ethnic groups, does not extend to those of Caucasian ethnicity. In their review, Notaras et al [11] indicate how the functional 10 The rs6265 polymorphism has been studied extensively in schizophrenia and, although the majority of studies find no substantial or significant effect, a metaanalysis [20] indicated that the Met66Met or AA genotype confers a 19% increase in risk for schizophrenia.…”

“…Associations with METH dependence have been reported [13,14], albeit not in all ethnic groups [15,16], as well as with responses to amphetamine infusion [17]. Therefore, the purpose of this study was to determine the association of rs6265 with METH dependence and METH-induced psychosis in the Thai population.…”

COMT Associations with Disordered Gambling and Drinking Measures

“…Perhaps individuals with lower subcortical phasic DA release (e.g., Met homozygotes) tend to attribute less salience to stimuli (particularly reward-related stimuli) and consequently tend to seek out more immediately rewarding stimuli such as drugs, which strongly activate and sensitize the DA system (Berridge 2007). However, the Met/Met genotype thus far has not been associated with the use of other substances (Bousman et al 2010; Vandenbergh et al 1997), although the Met allele has been associated with heaviness of smoking (Munafo et al 2011). …”

Gender, Brain-Derived Neurotrophic Factor Val66Met, and Frequency of Methamphetamine Use

“…The Val allele (higher BDNF secretion) is associated with MA dependence in Chinese males 39, 40 but not Caucasian males 41 or in a predominantly male Japanese sample 42 but whether BDNF Val66Met is associated with MA dependence in females is not known. In a human lab study among healthy adults, Val/Val homozygotes reported greater amphetamine subjective effects (arousal and energy) relative to Met carriers 43 while we previously reported better outcomes of treatment for MA dependence among Caucasians with Val/Val genotype 44 .…”