Dataset Information

Association of PIP4K2A Polymorphisms with Alcohol Use Disorder.

ABSTRACT: Alcohol use disorder (AUD) not only influences individuals and families but also has a lasting social impact on communities at the national level. Dopaminergic neurotransmission is involved in excessive alcohol consumption. Phosphatidylinositol-5-phosphate-4-kinase type 2 α (PIP4K2A) plays an important role in the regulation of ascending dopamine pathways. In this study; we determined possible associations between nine polymorphisms in PIP4K2A and AUD in Russian men. 279 Russian men with AUD were investigated. The control group consisted of 222 healthy men from the general Russian population. Genotyping of DNA samples for nine polymorphic variants of PIP4K2A was carried out by the Applied Biosystems™ QuantStudio™ 5 Real-Time PCR System with use of the TaqMan1 Validated SNP Genotyping Assay (Applied Biosystems; CIIIA). Carriage of the PIP4K2A rs2230469*TT/T genotype/allele was a relative risk factor for developing AUD in men (p = 0.026 and p = 0.0084 accordingly). Moreover; men with AUD had a higher frequency of PIP4K2A rs746203*T allele (p = 0.023) compared to healthy men. For the first time; we demonstrated different PIP4K2A polymorphisms to be associated with AUD presumably due to dopamine system modulation resulting from regulation of the lateral habenula.

SUBMITTER: Fedorenko OY

PROVIDER: S-EPMC8535504 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Association of <i>PIP4K2A</i> Polymorphisms with Alcohol Use Disorder.

Fedorenko Olga Yu OY Mikhalitskaya Ekaterina V EV Toshchakova Valentina A VA Loonen Anton J M AJM Bokhan Nikolay A NA Ivanova Svetlana A SA

Genes 20211019 10

<h4>Background</h4>Alcohol use disorder (AUD) not only influences individuals and families but also has a lasting social impact on communities at the national level. Dopaminergic neurotransmission is involved in excessive alcohol consumption. Phosphatidylinositol-5-phosphate-4-kinase type 2 α (PIP4K2A) plays an important role in the regulation of ascending dopamine pathways. In this study; we determined possible associations between nine polymorphisms in <i>PIP4K2A</i> and AUD in Russian men.<h4 ...[more]

PMID: 34681036

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Project description:BackgroundBrain-derived neurotrophic factor (BDNF) has been proposed to play a role in chronic alcohol consumption. However, studies investigating the association of single nucleotide polymorphisms (SNPs) in the BDNF gene with alcohol use disorder (AUD), including alcohol dependence, have obtained inconsistent results. This meta-analysis aims to examine the role of BDNF SNPs (rs6265, rs16917204, rs7103411, and rs11030104) in the risk of AUD.Materials and methodsA multidatabase search identified 17 articles (20 studies) for inclusion. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate associations using standard genetic models (homozygous, recessive, dominant, and codominant). Significant associations were defined as those with a p-value ≤ 0.05 after applying the Bonferroni correction (pBC). Subgroup analysis was conducted based on ethnicity (Caucasian and Asian populations). Sources of heterogeneity were investigated through outlier treatment and meta-regression analysis. Only significant outcomes were further subjected to sensitivity analysis and assessment of publication bias.ResultsThis meta-analysis generated four significant pooled ORs, representing the core outcomes, all of which indicated reduced risks. Overall, the results indicated a significant association between the BDNF polymorphism and the risk of AUD in homozygous (OR = 0.72, 95% CIs = 0.60-0.85, pBC = 0.0038) and codominant (OR = 0.84, 95% CIs = 0.78-0.91, pBC = 0.0019) model. In subgroup analysis by ethnicity, homozygous (OR = 0.59, 95% CIs = 0.44-0.78, pBC = 0.0057) and recessive (OR = 0.61, 95% CIs = 0.46-0.81, pBC = 0.0133) models of BDNF polymorphisms were significantly associated with a reduced risk of AUD in Caucasians. However, no significant associations were found in Asians. Meta-regression analysis did not identify any covariates that significantly contributed to the observed heterogeneity. The core significant associations were robust and showed no evidence of publication bias.ConclusionThe current meta-analysis suggests that the examined BDNF SNPs have a protective effect in the overall analysis (homozygous and codominant) and in the Caucasians subgroup (homozygous and recessive) while the Asians exhibited no effects of BDNF SNPs on AUD. BDNF polymorphisms might serve as a protective factor against the risk of AUD and could be useful markers in the clinical genetics of AUD.

Project description:<p>The Australian twin-family study of alcohol use disorder (OZALC study) derives from telephone diagnostic interview studies of two general population volunteer cohorts of Australian twins (cohort 1, mostly born 1940-1964; cohort 2, born 1964-71) and the spouses of the former cohort - a total of over 11,000 families. Three coordinated studies, using a shared assessment protocol and with a shared goal of gene-discovery, were conducted - one funded by the National Institute on Drug Abuse, the others by the National Institute on Alcoholism and Alcohol Abuse - by investigators associated with the Midwest Alcoholism Research Center at Washington University in St. Louis, and investigators at Queensland Institute of Medical Research, Brisbane, Australia (led by Professor Nicholas Martin), using informative families identified from these cohorts. The first of these (NIDA Nicotine Addiction Genetics [NAG] project, PI Pamela Madden) identified index cases from the 3 cohorts with a history of heavy smoking (smoked 20 or more cigarettes daily, or 40 or more cigarettes on 1 or more occasions) and with additional available full siblings who were smokers, and interviewed and obtained blood samples from twins, and cooperative full siblings and parents, in order to identify families that would be informative for linkage analysis of a quantitative heaviness of smoking trait. The second identified additional families with an index case who either reported a history of alcohol dependence (DSM-IV), or scored above the 85th percentile on a quantitative measure of heaviness of alcohol use (alcohol factor score), derived from measures of frequency of heavy drinking, frequency of drinking to intoxication, and typical weekly consumption in standard drinks (all referenced to the respondent's heaviest drinking period) and of lifetime maximum 1-day alcohol consumption and maximum tolerance to alcohol (drinks before getting drunk or before feeling effects of alcohol). Interview and DNA were obtained from index cases and siblings, and DNA only from available parents. The goal of this second study (NIAAA OZ-ALCOHOL EDAC study, PI Andrew Heath) was to identify sibships including pairs who were either extreme concordant for the quantitative consumption measure (both scoring above the 85th percentile) or extreme discordant (one scoring above the 85th percentile and one scoring below the 30th percentile) that would be informative for linkage analysis. The third identified additional sibships solely on the basis of large sibship size, regardless of alcohol or tobacco use phenotypes (NIAAA OZ-BIGSIB study, PIs the late Richard Todd, Andrew Heath). From these coordinated studies a case-control series of alcohol dependent individuals and unaffected controls were constructed for a family-based Genomewide Association Study (OZALC-GWAS) of heaviness of alcohol use and alcohol dependence, funded by the National Institute of Alcoholism and Alcohol Abuse. These data are made available here for all investigators studying outcomes related to alcohol or tobacco use (including major depressive disorder).</p>

Project description:BackgroundExtensive research indicates that having a positive family history of alcohol use disorder (FHP) and impulsivity are 2 risk factors for problem drinking. To our knowledge, no study has investigated which facets of impulsivity interact with family history to increase risk for problem drinking. The goal of this study was to: (i) examine whether FHP individuals with higher levels of impulsivity are more likely to engage in problematic drinking, and (ii) identify which facets of impulsivity interact with FHP to increase risk for problems.MethodsThe data consisted of a combined sample of 757 participants (50% female, 73% White, mean age = 32.85, SD = 11.31) drawn from the Transdisciplinary Tobacco Use Research Center and the Center for the Translational Neuroscience of Alcohol. Analyses of covariance and cumulative logistic regression models investigated the association of family history and impulsivity-related traits with drinking quantity, frequency, and alcohol-related problems. Models were adjusted for age, sex, race, ethnic group, education level, and data source.ResultsSignificant interactions between impulsivity and family history were found for measures of alcohol-related problems. Specifically, there was a stronger positive association of Barratt Impulsiveness Scale (BIS) poor self-regulation with interpersonal, F(1, 504) = 6.27, p = 0.01, and impulse control alcohol-related problems, F(1, 504) = 6.00, p = 0.01, among FHP compared to FHN individuals. Main effects of family history and impulsivity on alcohol quantity and frequency of use and problems were also found.ConclusionsThese findings suggest that having both a family history of AUD and high BIS poor self-regulation is more strongly associated with alcohol-related consequences in the interpersonal and impulse control domains. Given the heterogeneity of impulsivity, these findings highlight the need for additional research to examine which facets of impulsivity are associated with which alcohol outcomes to narrow phenotypic risk for alcohol misuse.

Dataset Information

Association of PIP4K2A Polymorphisms with Alcohol Use Disorder.

Publications

Association of <i>PIP4K2A</i> Polymorphisms with Alcohol Use Disorder.

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