Influence of DAT1 Promotor Methylation on Sports Performance

In the mammalian genome, DNA methylation is an epigenetic mechanism involving the transfer of a methyl group onto the C5 position of the cytosine to form 5-methylcytosine. DNA methylation regulates gene expression by recruiting proteins involved in gene repression or by inhibiting the binding of transcription factors (TFs) to DNA. As there are still many questions concerning the role of methylation in creating personality, we concentrated on searching for such associations. The research group was 100 sports male subjects (mean age = 22.88, SD = 6.35), whereas the control group included 239 healthy male volunteers matched for age (mean age = 21.69, SD = 3.39), both of European origin. The methods used in our research were as follows: DNA isolation, methylation-specific PCR, sequencing chromatophores, all conducted according to the manufacturer’s procedure. To evaluate personality traits, the NEO Five-Factor Personality Inventory (NEO-FFI) and STAI Inventory were used. We observed the existence of a statistically significant correlation for all the aspects of personality covered and CpG islands’ methylation. Nonetheless, we think that the tested group and the number of tested promotor islands in the DAT1 gene are still too small to make explicit conclusions, so it needs further profound analysis.

Involvement of DAT1 Gene on Internet Addiction: Cross-Correlations of Methylation Levels in 5′-UTR and 3’-UTR Genotypes, Interact with Impulsivity and Attachment-Driven Quality of Relationships

Internet influences our communication, social and work interactions, entertainment, and many other aspects of life. Even if the original purpose was to simplify our lives, an excessive and/or maladaptive use of it may have negative consequences. The dopamine transporter (DAT1) gene was studied in relation to addictions, including excessive use of the Internet. The crucial role of DAT1 was previously underlined in modulating emotional aspects, such as affiliative behaviors. The present research follows a new approach based on cross-correlation between (de)methylation levels in couples of CpG loci, as previously shown. We investigated the possible relationships between Internet addiction, impulsivity, quality of attachment, DAT1 genotypes (from the 3′-untranslated region (UTR) variable number of tandem repeats (VNTR) poly-morphism), and the dynamics of methylation within the 5’-UTR of the DAT1 gene. From a normative sample of 79 youths, we extrapolated three subgroups a posteriori, i.e., one “vulnerable” with high Internet Addiction Test (IAT) scores (and high Barrat Impulsivity Scale (BIS) scores; n = 9) and two “controls’’ with low BIS scores and 10/10 vs. 9/x genotype (n = 12 each). Controls also had a “secure” attachment pattern, while genotypes and attachment styles were undistinguished in the vulnerable subgroup (none showed overt Internet addiction). We found a strongly positive correlation in all groups between CpG2 and CpG3. An unsuspected relationship between the 3’-UTR genotype and a 5’-UTR intra-motif link was revealed by CpG5–CpG6 comparison. The negative correlation between the CpG3–CpG5 positions was quite significant in the control groups (both with genotype 10/10 and with genotype 9/x), whereas a tendency toward positive correlation emerged within the high IAT group. In conclusion, future attention shall be focused on the intra- and inter-motif interactions of methylation on the CpG island at the 5′-UTR of DAT1.

Determining the association between polymorphisms of the DAT1 and DRD4 genes with attention deficit hyperactivity disorder in children from Java Island

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurobehavioural in the children. Genetic factor is known one of the factors which contributed in ADHD development. VNTR polymorphism in 3’UTR exon 15 of DAT1 gene and exon 3 of DRD4 gene are reported to be associated in ADHD. In this study we examine the association of ADHD with VNTR polymorphism of DAT1 and DRD4 gene in Indonesian children. Sixty-five ADHD children and 70 normal children (6- 13 years of age), were included in the study, we matched by age and gender. ADHD was diagnosed by DSM-IV. We performed a casecontrol study to found the association between ADHD and VNTR polymorphism of DAT1 and DRD4 genes. The 10-repeat allele of DAT1 and 2-repeat allele of DRD4 were higher in Indonesian children. Although the frequency of these allele was higher, but it was similar both in ADHD and control groups. Neither DAT1 nor DRD4 gene showed showed significant difference in genotype distribution and frequency allele between both groups (p > 0.05). No association between ADHD and VNTR polymorphism of DAT1 and DRD4 genes found in Indonesian children. This data suggest that DAT1 and DRD4 do not contribute to etiology of ADHD in Indonesian children. Further studies are needed to clarify association between VNTR polymorphism of DAT1 and DRD4 genetic with ADHD of Indonesian children in larger sample size and family based study.

Contribution of Dopamine Transporter Gene Methylation Status to Cannabis Dependency

The susceptibility to cannabis dependency results from the influence of numerous factors such as social, genetic, as well as epigenetic factors. Many studies have attempted to discover a molecular basis for this disease. However, our study aimed at evaluating the connection between altered methylation of the dopamine transporter gene (DAT1) promoter CpG sites and cannabis dependency. In the cases of some DNA sequences, including the DAT1 gene region, their methylation status in blood cells may reflect a systemic modulation in the whole organism. Consequently, we isolated the DNA from the peripheral blood cells from a group of 201 cannabis-dependent patients and 285 controls who were healthy volunteers and who were matched for age and sex. The DNA was subjected to bisulfite conversion and sequencing. Our analysis revealed no statistical differences in the general methylation status of the DAT1 gene promoter CpG island between the patients and controls. Yet, the analysis of individual CpG sites where methylation occurred indicated significant differences. These sites are known to be bound by transcription factors (e.g., SP1, p53, PAX5, or GR), which, apart from other functions, were shown to play a role in the development of the nervous system. Therefore, DAT1 gene promoter methylation studies may provide important insight into the mechanism of cannabis dependency.

The study of the genetic component of eating behavior in a sample of obese Yakuts

Характер питания коренных жителей Севера сменился с белково-липидного на углеводно-липидный. Среди них увеличилось число лиц, страдающих ожирением, обусловленном не только сменой характера питания, но и гиподинамией. Целью исследования является изучение генетической составляющей нарушения пищевого поведения в выборке якутов с ожирением. Всего в исследовании принял участие 191 человек якутской национальности, из них 100 пациентов страдающих ожирением различной степени тяжести (73 женщины и 27 мужчин), в качестве группы сравнения сформирована выборка людей с нормальными показателями ИМТ (< 25) в количестве 91 человека (70 женщин и 21 мужчина). По результатам исследования, частота встречаемости мутантного аллеля А rs9939609 гена FTO во всей обследованной группе составила 27%, при этом доля лиц с генотипом АА составляла 9,4 %. Анализ распределения аллелей и генотипов полиморфизма rs27072 гена DAT1 показал преобладание предкового аллеля G (90,8 %) и генотипа GG (82,7 %) во всех обследованных группах. The nature of the nutrition of the inhabitants of the North is from lipo-lipid. Among them, the number of obese people increased, due not only to the variable nature of nutrition, but also to physical inactivity. The aim of the study is to study the genetic component of eating disorders. In total, 191 people took part in the study, of which 100 people suffer from obesity of varying severity (73 women and 27 men), which allows us to compare a sample of people with normal MMT ((25) in the amount of 91 people (70 women and 21 men). According to the results of studies, the frequency of occurrence of the mutant allele A of rs9939609 FTO gene in all the studied groups is 27%, while the AA genotype is only 9.4%. An analysis of the distribution of alleles and genotypes of rs27072 polymorphism of the DAT1 gene showed the predominance of the ancestral G allele (90.8%) and the GG genotype (82.7%) in all examined samples.