Serotonin transporter gene promoter polymorphism (5-HTTLPR) and alcohol use in general population: interaction effect with birth cohort.

RATIONALE AND OBJECTIVE: Prevalence of alcohol use is markedly influenced by socioeconomic conditions and is therefore subject to cohort effects. The common genetic variation 5-HTTLPR (serotonin transporter gene-linked polymorphic region) has been related to several aspects of alcohol use and addiction but with mixed results, probably due to different environmental interaction effects. We aimed at assessing whether the association between alcohol use and 5-HTTLPR genotype is subject to cohort effects as birth cohorts may be raised in significantly different environments. METHODS: We used the database of the Estonian Children Personality Behaviour and Health Study (beginning in 1998). Cohorts of initially 9-year-old (recalled at ages 15 and 18) and 15-year-old (recalled at ages 18 and 25) children provided self-reports on their alcohol use in all data collection waves (complete data available n = 1,075). RESULTS: A significant genotype × gender × cohort interaction effect on the age of consuming the first alcoholic drink was found [F(2, 1,063) = 7.2, p < 0.001]. Females with the s/s genotype in the older cohort were the latest experimenters with alcohol, while the s/s females of younger cohort had tried alcohol earlier than any other group. In males, there was no significant cohort × genotype interaction, but the 5-HTTLPR genotype was associated with alcohol use, the s/s subjects reporting the highest consumption. CONCLUSION: Expression of genetic vulnerability to alcohol use is influenced by birth cohort effects. The 5-HTTLPR genotype is associated with alcohol consumption in general population, but the effect depends on gender and birth cohort.

A 10-year serological follow-up of celiac disease in an Estonian population.

BACKGROUND: Celiac disease (CD) is induced by wheat gluten and related prolamines. Its prevalence may be underestimated in many geographic regions and populations, and has recently increased in several countries. In 1998 and 1999, a random sample of Estonian schoolchildren was screened with IgA-type tissue transglutaminase antibodies (IgA-tTG) for CD. The results revealed a CD prevalence of 0.34%, which is lower compared with many other European countries. OBJECTIVE: We rescreened the same population for CD using IgA-tTG after a 10-year interval. MATERIALS AND METHODS: A total of 891 patients from the initial sample were rescreened using the IgA-tTG assay for a participation rate of 76.8% (median age, 24.3 years). As in the initial study, the IgA-tTG results were evaluated by ImmunoCAP EliA Celikey using an IgG-tTG and deamidated gliadin antibody assay for IgA-deficient cases. RESULTS: No new cases of CD were found in this follow-up study. Of note, 75% of patients with initial IgA-tTG-positive results and biopsy-proven CD remained seropositive. One patient with a negative seroconversion at the time of rescreening followed a strict gluten-free diet during the follow-up years. CONCLUSION: In a 10-year follow-up period, no new cases of CD were found in this Estonian population of school-children and young adults. Therefore, we presume no increase in CD during the last decade among this age group in Estonia. Additional studies are needed to determine whether similar results would be obtained in other age groups, because of differences in the CD prevalence between Estonian and other European populations.

The relationship between serotonin transporter gene promoter polymorphism and serum lipid levels at young age in a longitudinal population-representative study.

The serotonin transporter gene promoter region polymorphism (5-HTTLPR) has been linked to psychiatric disorders, mostly anxiety and affective disorders. In elderly populations 5-HTTLPR polymorphism has also been reported to be associated with serum lipid levels. We have examined the interaction of the 5-HTTLPR polymorphism and the markers of lipid metabolism at young age in a longitudinal, population-representative cohort study. The sample of the Estonian Children Personality Behaviour and Health Study (initially cohorts of 9 and 15 year old children, complete lipid and genotype data for n=1176) was examined throughout 10 years. Subjects were genotyped and the levels of low-density lipoproteins, high-density lipoproteins, triglycerides, and total cholesterol were measured. Children and adolescents carrying the s allele of the 5-HTTLPR polymorphism had lower levels of low-density lipoprotein and total cholesterol. At the age of 25, the s allele carriers had higher levels of high-density lipoproteins. These associations were independent of gender. Thus the 5-HTTLPR can be associated with the serum lipid levels and in particular low-density lipoproteins already in a young age.

Effects of serotonin transporter promoter and BDNF Val66Met genotype on personality traits in a population representative sample of adolescents.

The purpose of this study was to investigate the effects of the 5-HTTLPR and brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms on self-reported Big Five personality traits and their facets in a population representative sample of adolescents. The sample consisted of both cohorts of the Estonian Children Personality Behaviour and Health Study, and personality data were collected during its second waves. The 5-HTTLPR and BDNF Val66Met polymorphisms were genotyped. The BDNF Val66Met had a significant effect on conscientiousness [F(1,807)=4.32, P=0.038]. We did not find effects of the 5-HTTLPR polymorphism on the main domains of personality, however, a gene×gene interaction on conscientiousness emerged -BDNF Val66Met Met-allele carriers with the 5-HTTLPR s/s genotype had by far the lowest scores in conscientiousness [F(2,803)=4.38, P=0.012]. In addition, we found genotype effects on some facet scales. In conclusion, the BDNF Val66Met genotype Met-allele carriers have lower conscientiousness, and this effect is increased in the 5-HTTLPR s/s individuals.

Effects of the serotonin transporter (5-HTTLPR) and α2A-adrenoceptor (C-1291G) genotypes on substance use in children and adolescents: a longitudinal study.

RATIONALE AND OBJECTIVE: Twin studies suggest that substance use initiation in children and adolescents is determined primarily by environmental influences, whereas the establishment of use patterns is strongly controlled by genetic factors. The present study analysed the effects of the serotonin transporter promoter polymorphism [5-HT transporter gene-linked polymorphic region (5-HTTLPR)] and the α(2A)-adrenoceptor C-1291G genotype (ADRA2A C-1291G) as well as their interaction effects on alcohol, tobacco and drug use from preadolescence to the late adolescence. METHODS: Initial sample of 9-year-old children of Estonian Children Personality Behaviour and Health Study (n = 583) was recalled at ages 15 and 18. Participants reported in all waves how frequently they smoked and used alcohol and illicit drugs. RESULTS: 5-HTTLPR had age-dependent effects on alcohol, tobacco and drug use: substance use did not differ by genotype at age 9, but at age 15, the participants with the short (s)/s genotype had higher tobacco use, and at age 18, they were more active alcohol, drug and tobacco users. Effects of ADRA2A C-1291G on drug use were dependent on gender, age and 5-HTTLPR. Males (age 18) with ADRA2A CG genotype, when compared to other participants, tended to have higher drug use especially when they had s/s genotype of 5-HTTLPR. CONCLUSIONS: Our results reveal that expression of genetic vulnerability for substance use in children and adolescents may depend on age, gender, interaction of genes, and type of substance.

Personality and the serotonin transporter gene: Associations in a longitudinal population-based study.

Associations between the promoter polymorphism of the serotonin transporter gene (5-HTTLPR) and anxiety-related personality traits in healthy adult subjects have been inconsistent. We assessed personality in participants of the Estonian Children Personality Behaviour and Health Study, using parental reports and self-reports. In the younger cohort, according to parental assessments at ages 9 and 15, children homozygous for the S allele had significantly higher scores of Neuroticism and lower scores of Openness, Agreeableness and Conscientiousness. Parental assessment of the older cohort at ages 15 and 18 did not yield any genotype effect on personality; however, interaction of cohort and genotype was not significant. According to self-reports, SS homozygotes had higher Neuroticism at age 15 but not at age 18. Thus, homozygocity for the S allele of the 5-HTTLPR is related to anxiety-related personality traits in general population, but this is easier to detect before adolescence.

The transcription factor TFAP2B is associated with insulin resistance and adiposity in healthy adolescents.

Insulin resistance and central adiposity are strong risk indicators for type 2 diabetes and coronary heart disease. An important role for adipose tissue in the etiology and progression of these conditions has recently become more evident. A transcription factor, TFAP2B, has been shown to participate in the regulation of adipocyte metabolism, by facilitating glucose uptake and lipid accumulation, while simultaneously reducing insulin sensitivity, and recently a direct function for TFAP2B as an inhibitor of adiponectin expression was observed. In this study, we have investigated how insulin resistance, plasma adiponectin, and central adiposity, in a normal population of adolescents, are affected by genetic variability in TFAP2B. Our results show that both insulin sensitivity, as measured from levels of fasting glucose and insulin, and central adiposity, estimated by subscapular skinfold thickness, were significantly associated to genetic variability in TFAP2B. This association was restricted to males only, where carriers of the 4-repeat allele of intron 2 had higher insulin sensitivity and lower subscapular skinfold thickness. Levels of adiponectin did not show any association to the TFAP2B polymorphism, but was negatively correlated to central adiposity in females. These results suggest that reduction of TFAP2B expression could have a protective effect against future risk of complications associated with decreased insulin sensitivity and central adiposity, such as type 2 diabetes and coronary heart disease.

Associations between an alpha 2A adrenergic receptor gene polymorphism and adolescent personality.

The aim of this study was to investigate the impact of the C-1291G polymorphism in the promoter region of the alpha 2A adrenoreceptor gene (ADRA2A) to the personality traits. In the present study, data of the younger cohort of the Estonian Children Personality Behaviour and Health Study was used (N = 419). Personality traits were assessed by 240-item (Estonian Personality Item Pool NEO (EPIP-NEO)). Restriction enzyme MspI was used after PCR amplification to genotype the subjects according to C-1291G polymorphism of the ADRA2A. There were no significant differences on the level of the Big Five personality domains between genotypes; however, there were three significant differences on the level of different subscales. The subjects with GG genotype had significantly higher scores on Depression and significantly lower scores on Morality and Orderliness compared to subjects with CC and CG genotypes. There was a significant interaction between sex and ADRA2A polymorphism regarding E1, Friendliness; E2, Gregariousness; and E6, Cheerfulness. With CC and CG genotypes girls had higher scores on extraversion scales than boys, but with GG genotype boys score higher than girls with GG genotype. It is concluded that the gene polymorphism in the ADRA2A has an influence on personality traits in adolescents.

Agreement among adolescents, parents, and teachers on adolescent personality.

Agreement between adolescents, mothers, fathers, and teachers on adolescents' personality traits was investigated in a longitudinal study. The targets for personality ratings were the adolescents who participated in the European Youth Heart Study in Estonia. There were 593 participants in the first wave and 480 participants in the follow-up study 3 years later. Adolescents' self-reports as well as father, mother, and teacher ratings were collected using questionnaires to measure the five-factor model of personality. In both waves, inter-rater agreement was highest between mothers and fathers, was low to moderate for parent-self ratings, and was lowest for ratings between self and teacher, mother and teacher, and father and teacher. Test-retest correlations were moderate for parent and self-ratings but failed to reach statistical significance for three of the five teacher-rated traits, suggesting lower reliability of teacher ratings. Possible explanations for the low agreement between teachers and other judges are discussed.

Changes in platelet monoamine oxidase activity, cholesterol levels and hyperactive behaviour in adolescents over a period of three years.

Platelet monoamine oxidase (MAO) activity is a peripheral marker of central serotonergic activity, and has been associated with aggressive, impulsive and hyperactive behaviour, alcohol and drug abuse. Central serotonergic activity has also been associated with plasma cholesterol levels. In the present longitudinal investigation in adolescents (n = 320) changes in platelet MAO activity and in plasma cholesterol levels over three years were measured, and their possible association with changes in aggressive and hyperactive behaviour, smoking, alcohol and drug use was studied. The measures were taken at age 15 and 18 years. Psychological data were obtained from teachers by using the Hyperactivity Scale [B. af Klinteberg, Studies on Sex-related Psychological and Biological Indicators of Psychosocial Vulnerability: A Developmental Perspective, University of Stockholm, Department of Psychology, 1988]. The results of the study show that in most of the tested individuals, platelet MAO activity is a relatively stable measure, however, there was a significant number of subjects with a noticeable change in MAO activity. In subjects with decreased platelet MAO activity, total and HDL cholesterol levels were significantly increased. Also, changes in HDL cholesterol and in platelet MAO activity were inversely associated with changes in the score of Concentration Difficulties. The changes in platelet MAO activity and cholesterol level were not associated with alcohol and drug use among the subjects. This longitudinal analysis provides preliminary evidence that changes in platelet MAO activity and cholesterol, which may reflect changes in central serotonergic activity are associated with attention deficit in adolescents.

Association between substance use, personality traits, and platelet MAO activity in preadolescents and adolescents.

This study examined the relationship between alcohol/illicit drug use, the Five-Factor Model (FFM) personality traits, aggressiveness (Agg), and hyperactivity (Hyp), and platelet monoamine oxidase (MAO) activity in a population-derived representative sample of preadolescents and adolescents (n=1172). Alcohol and illicit drug use was self-reported. The FFM personality inventories were filled in by mothers of the participants, and Agg and Hyp were rated by their class teachers. Higher scores in extraversion (E), Agg, and Hyp and lower scores in conscientiousness (C) together with older age were significant predictors of more frequent alcohol use in adolescents. No significant association was found between alcohol illicit drug use, and platelet MAO activity.