Association between DRD2/ANKK1 TaqIA allele status and striatal dopamine D2/3 receptor availability in alcohol use disorder

The association between blunted dopaminergic neurotransmission and alcohol use disorder (AUD) is well-known. In particular, the impairment of postsynaptic dopamine 2 and 3 receptors (DRD2/3) in the ventral and dorsal striatum during the development and maintenance of alcohol addiction has been investigated in several positron emission tomography (PET) studies. However, it is unclear whether these changes are the result of adaptation or genetic predisposition. Here we investigated the association between DRD2/ankyrin repeat and kinase domain-containing 1 (ANKK1) TaqIA allele (rs1800497) status and striatal DRD2/3 availability measured by 18F-fallypride PET in 13 AUD patients and 17 sex-matched healthy controls. Age and smoking status were included as covariates. Contrary to our expectations, TaqIA allele status was not associated with striatal DRD2/3 availability in either group and there was no significant difference between groups, possibly due to the relatively small sample size (N=30). Nonetheless, this is the first in vivo study investigating the relationship between dopamine receptor availability and genetic factors in AUD. The pitfalls of assessing such relationships in a relatively small sample are discussed.

A-5 Brain-Derived Neurotrophic Factor Val66Met and Neuropsychological Functioning Following Early Childhood Traumatic Brain Injury

Objective The present study examined the differential effect of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on neuropsychological functioning in children with traumatic brain injury (TBI) relative to children with orthopedic injury (OI). Method Participants were drawn from a prospective, longitudinal study of children who sustained a TBI (n = 69) or OI (n = 72) between 3 and 7 years of age. Children completed a battery of neuropsychological measures targeting attention, memory, and executive functions at four time points spanning the immediate post-acute period to 18 months post-injury. Children also completed a comparable age-appropriate battery of measures approximately 7 years post-injury. Parents rated children’s executive functioning at all time points. Results Longitudinal mixed models revealed a significant allele status x injury group interaction for verbal fluency (p = 0.007) and a non-significant trend for parent-rated dysexecutive behaviors (p = 0.069), and cross-sectional models at 7 years post-injury revealed a non-significant trend for the allele status x injury group interaction for fluid reasoning skills (p = 0.074). Post hoc analyses suggested a consistent pattern of poorer neuropsychological functioning in Met carriers relative to Val/Val homozygotes in the TBI group; in contrast, the opposite trend was observed in the OI group. Conclusions The results suggest a differential effect of the BDNF Val66Met polymorphism on verbal fluency, dysexecutive behaviors, and fluid reasoning skills in children with early TBI relative to OI, and that the Met allele—associated with reduced activity-dependent secretion of BDNF—confers risk for poorer neuropsychological functioning in children with TBI.

Apolipoprotein E e4 allele status and later-life depression in the Lothian Birth Cohort 1936

Background Previous results have been mixed regarding the role of the apolipoprotein E e4 (APOE e4) allele in later-life depression: some studies note that carriers experience greater symptoms and increased risk while others find no such association. However, there are few prospective, population-based studies of the APOE e4-depression association and fewer that examine depressive symptom trajectory and depression risk longitudinally. We examined the association between APOE e4 allele status and longitudinal change in depressive symptoms and depression risk in later-life, over a 12-year follow-up period. Methods We used data from 690 participants of the Lothian Birth Cohort 1936 who took part in the Scottish Mental Survey 1947 (aged 11) and were followed-up in later-life over five waves from 2004 to 2019 (aged 70–82). We used APOE e4 allele status to predict longitudinal change in depressive symptom scores and risk of depression (defined by a symptom score threshold or use of depression-related medication). Models were adjusted for sex, childhood cognitive ability, childhood social class, education, adult social class, smoking status and functional limitations at baseline. Results Depressive symptom scores increased with age. Once adjusted for covariates, APOE e4 allele status did not significantly predict symptom score trajectories or depression risk. Greater functional limitations at baseline significantly predicted poorer symptom score trajectories and increased depression risk (defined by medications). APOE e4 allele status did not significantly moderate the contribution of sex, education or functional limitations. Conclusions There was no evidence that APOE e4 carriers experience an increased risk for later-life depression.

Ethical Aspects of Genotype Disclosure: Perceptions of Participants in a Nutrigenetic Study in Finland

<b><i>Objective:</i></b> The aim of this study was to gain insight into the understanding of genetics and perceptions on the ethical issues related to genotype disclosure of the participants in a nutrigenetic study. <b><i>Methods:</i></b> A close-ended questionnaire was developed based on literature and discussions among the research group members. The questionnaire contained a ­total of 33 questions, which were divided into 4 categories – demographics, knowledge assessment, concerns related to participation, and opinions on disclosure of information. Majority of the participants (250 out of 281) of a nutrigenetic study, in which effect of disclosing <i>APOE</i> allele status on lifestyle changes was studied, completed the questionnaire online following the informed consent process. The responses from the knowledge assessment and the concern categories were transformed into knowledge and concern scales, respectively, and analysed by descriptive statistical methods. The statistical associations between the categorical variables were determined using χ² test of independence. The relationship between the continuous variables was assessed using Pearson product-moment correlation coefficient and internal consistency of questions by Cronbach’s alpha. <b><i>Results:</i></b> No correlation was observed between the level of education and knowledge scores. About 10% of the participants thought that the genetic predisposition would be stressful to them and their family members. <b><i>Conclusions:</i></b> Careful distribution of information before a nutrigenetic study supports understanding and reduces concerns of genetic susceptibility. In Finland, strong basic education is likely to have strengthened the trust in research process.

FEATURES OF ALLELIC POLYMORPHISM OF PROLACTIN AND BETA-LACTOGLOBULIN GENES IN LACON SHEEP

The paper presents prolactin (PRL) and beta-lactoglobulin (β-LG) gene polymorphism in the Lacaune sheep, bred at Nikolaev peasant farm enterprise, Krasnodar Krai. Genetic and statistical analysis allowed to determine numerical values of the genetic constants. The genetic structure of the population under study and its distinctness, determined both by breed affi liation and by allele status of the genes, was assessed.

The study of VvMybA1 allele status of the indigenous grapevine varieties with non-colored berries

In the present work we describe preliminary results on a partial VvMybA1 locus sequencing of rear indigenous grapevine varieties. Obtained sequences were mostly conservative and have matches in NCBI GenBank. As expected, most of them have a sequence that is typical for varieties with non-colored berries. Surprisingly, however, cultivar Jaj izium biely demonstrated structure typical for varieties with colored berries, which implies another reason for the loss of color. Obviously, Tavlinskii pozdnii and Sypun chernyj varieties had typical for colored cultivars allele structure. Some nucleotide substitutions and differences in structure of sequences were found. Furthemore, we submitted our sequences to the NCBI and here we present their accession numbers: Unji bely (MW633123), Voskeat (MW633125), Tsolikauri (MW633126), Shabash (MW633127), Terbash (MW633130), Bajan Shirei (MW633131), Katta Kurgan (MW633132), Sirgula (MW633135), Khatmi (MW633136), Jaj izium biely (N/A), Tavlinskii pozdnii (MW633139), Sypun chernyj (MW633151). All sequences, excluding Jaj izium biely genotype, were submitted to the GenBank and will be available to the public as soon as possible.

The Association between Polygenic Hazard and Markers of Alzheimer’s Disease Following Stratification for APOE Genotype

Background: Research indicates that polygenic indices of risk of Alzheimer’s disease are linked to clinical profiles. Objective: Given the “genetic centrality” of the APOE gene, we tested whether this held true for both APOE-ε4 carriers and non-carriers. Methods: A polygenic hazard score (PHS) was extracted from 784 non-demented participants recruited in the Alzheimer’s Disease Neuroimaging Initiative and stratified by APOE ε4 status. Datasets were split into sub-cohorts defined by clinical (unimpaired/MCI) and amyloid status (Aβ+/Aβ-). Linear models were devised in each sub-cohort and for each APOE-ε4 status to test the association between PHS and memory, executive functioning and grey-matter volumetric maps. Results: PHS predicted memory and executive functioning in ε4ε3 MCI patients, memory in ε3ε3 MCI patients, and memory in ε4ε3 Aβ+ participants. PHS also predicted volume in sensorimotor regions in ε3ε3 Aβ+ participants. Conclusion: The link between polygenic hazard and neurocognitive variables varies depending on APOE-ε4 allele status. This suggests that clinical phenotypes might be influenced by complex genetic interactions.