NPY leu7pro and Alcohol Dependence in Finnish and Swedish Populations

Zhu, Guoqiang; Pollak, Lotta; Mottagui‐Tabar, Salim; Wahlestedt, Claes; Taubman, Julie; Virkkunen, Matti; Goldman, David; Heilig, Markus

doi:10.1111/j.1530-0277.2003.tb02715.x

Cited by 60 publications

(21 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In humans, linkage to the chromosomal region containing the NPY gene has been demonstrated 47, and there have been associations of NPY variation with both alcohol consumption 40 and dependence 48, 49. Other studies, however, have failed to replicate this association 50–52. Of note, our present study did not find any effects of rh NPY −1002T>G on alcohol consumption in normally reared animals, even following repeated alcohol exposure.…”

Section: Commentcontrasting

confidence: 44%

FunctionalNPYVariation as a Factor in Stress Resilience and Alcohol Consumption in Rhesus Macaques

Lindell¹,

Schwandt²,

Sun³

et al. 2010

Arch Gen Psychiatry

Self Cite

View full text Add to dashboard Cite

Context Neuropeptide Y (NPY) is important to countering stress and is involved in neuroadaptations that drive escalated alcohol drinking following repeated alcohol exposure in rodents. In humans, haplotype-driven diminution in NPY expression is predictive of amygdala response and emotional reactivity to stress. Genetic variation that affects the NPY system could impact resilience to stress and to developing addiction with continued alcohol use. Objective To determine whether functional NPY variation influences CSF NPY, behavioral adaptation to stress, and alcohol consumption in a nonhuman primate model of early adversity (peer rearing). Design We sequenced the rhesus macaque NPY locus (rhNPY) and performed in silico analysis to identify functional variants. We performed gel shift assays for a −1002 T>G using nuclear extract from testes, brain and hypothalamus. Levels of NPY in CSF were measured by RIA, and mRNA levels were assessed in amygdala using RT-PCR. During infancy, animals were exposed to repeated social separation stress, and tested for individual differences in alcohol consumption as young adults. Animals were genotyped for −1002 T>G, and the effects of this variant on mRNA expression, CSF NPY, behavior arousal during stress, and ethanol consumption were assessed by ANOVA. Results The G allele altered binding of regulatory proteins in all nuclear extracts tested, and −1002 T>G resulted in lower levels of NPY expression in amygdala. Macaques exposed to adversity had lower CSF NPY and exhibited higher levels of arousal during stress, but only as a function of the G allele. We also found that stress-exposed G allele carriers consumed more alcohol and exhibited an escalation in intake over cycles of alcohol availability and deprivation. Conclusions Our results suggest a role for NPY promoter variation in the susceptibility to alcohol use disorders and point to NPY as a candidate for examining GxE interactions in humans.

show abstract

Section: Commentcontrasting

confidence: 44%

FunctionalNPYVariation as a Factor in Stress Resilience and Alcohol Consumption in Rhesus Macaques

Lindell¹,

Schwandt²,

Sun³

et al. 2010

Arch Gen Psychiatry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Another report showed that European American men with alcoholism have a 5-5.5% Pro7 allele frequency, whereas the corresponding figure in nonalcoholic men was only 2% [155]. Subsequent studies, however, could not replicate this association [156]. A positive association between a novel polymorphism located in the 5 0 region of the NPY gene and alcohol dependence was recently identified in a Nordic population, but replication of their findings is yet to be published [157 ].…”

Section: Neuropeptide Y and Neuropeptide Y Receptorsmentioning

confidence: 99%

New findings on the genetic influences on alcohol use and dependence

Higuchi

Matsushita

Kashima

2006

Current Opinion in Psychiatry

View full text Add to dashboard Cite

Despite great advances in understanding of genetic vulnerability in alcohol use disorders, only two gene complexes, ADH and ALDH2, have been identified as having defined effects on alcohol use and liability to dependence in humans. New genes associated with increased risks for the disorder will certainly be added to this list in the near future. Neurobiological analyses of the effects of these genes will surely contribute to further understanding of the cause of alcohol dependence and the interindividual differences in risks.

show abstract

“…The lower frequency of the pro7 allele observed in Finnish type 2 alcoholic individuals indicated the protective effect of this allele against alcohol dependence [25]. In contrast, several studies have failed to show a significant association between the pro7 allele and alcohol dependence [34] or alcohol withdrawal symptoms [35]. A significant elevation in the T allele of NPY -C5671T was observed in Japanese alcohol-dependent subjects during withdrawal, but this significance vanished after Bonferroni correction [36].…”

Section: Discussionmentioning

confidence: 99%

Association between Neuropeptide Y Gene Polymorphisms and Alcohol Dependence: A Case-Control Study in Two Independent Populations

et al. 2013

View full text Add to dashboard Cite

Background: Alcohol dependence is a chronic, progressive neurobiological brain disorder. Previous research reported an inverse association between ethanol drinking and cerebral neuropeptide Y (NPY) levels. There are conflicting results of studies on NPY gene polymorphisms in association with alcohol dependence in humans. Methods: To assess the role of the NPY gene in alcohol dependence, we genotyped three polymorphisms - in a sample of 195 subjects from the Kota population (80 alcohol dependence and 115 controls) and 141 subjects from the Badaga population (80 alcohol dependence and 61 controls). Phenotype was defined based on the DSM-IV criteria. Genotyping was performed using sequencing. Association of the NPY gene with alcohol dependence was tested by using logistic regression and haplotype analyses and linkage disequilibrium. Results: All three polymorphisms were found to be in the Hardy-Weinberg equilibrium in both populations. The results of our study reveal a significant association between G1258A and alcohol dependence in both the Kota and Badaga populations. The linkage disequilibrium between the markers is not strong or significant. Haplotype analysis also did not show significant association between the NPY gene and alcohol dependence. Conclusion: These data support the hypothesis that alcohol dependence is influenced by the NPY G1258A polymorphism in Indian populations.

show abstract

NPY leu7pro and Alcohol Dependence in Finnish and Swedish Populations

Abstract: Pro7 does not seem to be associated with a diagnosis of alcoholism in Caucasian populations.

Cited by 60 publications

References 38 publications

FunctionalNPYVariation as a Factor in Stress Resilience and Alcohol Consumption in Rhesus Macaques

FunctionalNPYVariation as a Factor in Stress Resilience and Alcohol Consumption in Rhesus Macaques

New findings on the genetic influences on alcohol use and dependence

Association between Neuropeptide Y Gene Polymorphisms and Alcohol Dependence: A Case-Control Study in Two Independent Populations

Contact Info

Product

Resources

About