Background: An association between apolipoprotein E (apoE) gene polymorphism and temperament has been found in the Young Finns cohort. Motor activity in childhood and mental vitality, sociability and positive emotionality in adolescence were associated with apoE. Two research groups have attempted to replicate these findings but no associations have been found. Purpose: The purpose of the present study was to confirm the original findings with new and more reliable genotyping from a larger sample derived from the same Young Finns Study as the original finding.Methods: The study included 2808 participants aged 3 - 18 years in 1980. The same methods in assessing temperament were used as in the original study. Temperament was operationalized as motor activity, cooperativeness, negative emotionality, mental vitality, sociability and positive emotionality. Temperament was assessed by participants’ mothers in 1980 and 1983 and self-rated in 1983 by adolescent participants. Results: Motor activity was not associated with apoE polymerphisms. All other previous results were replicated. Adolescents’ positive emotionality, mental vitality and sociability were associated with apoE. Conclusions: The results indicated that there is an association between temperament and apoE. The previous absence of association between temperament and apoE in the replication studies may be due to the fact that researchers used different dimensions of temperament and thus probably studied different phenomena. Cultural differences in personality assessment might also explain the contradictory findings.
Apolipoprotein E (apoE) is a gene linked with coronary heart disease (CHD). A high prevalence of genotypes ε4/ 3 and ε4/4 has been meta-analytically associated with diagnosed CHD cases [
Two research groups have attempted to replicate these findings. Tsai, Yu and Hong [
The purpose of this study is to confirm the original finding of the Young Finns Study in a sample that consists of the participants in the original article [
The participants were drawn from an ongoing population-based prospective Young Finns Study which began in 1980. The original sample at the baseline comprised 3596 participants from six age cohorts, 3, 6, 9, 12, 15 and 18-year-olds, with different geographical and socioeconomic backgrounds. An equal number of urban and rural boys and girls were randomly chosen from the national population register to ensure national representativeness of the Finns, as comprehensively detailed previously [
All the 3596 participants were invited to participate in genotype and temperament assessments. ApoE genotypeing was conducted on 2946 persons who agreed to participate, of whom 2643 were genotyped by new methods and 303 had been genotyped earlier with an older method. The participants whose genotypes differed between the two measurement times were excluded from the analyses (n = 27) and thus apoE genotypes were available altogether on 2919 participants. Sufficient information on temperament was received from 2808 genotyped participants at the baseline in 1980 and from 2367 genotyped participants (52.6% women, 47.4% men) at the first follow-up in 1983. All the participants who had been successfully genotyped and had sufficient temperament data on any of the assessed temperament scales comprised the present study sample. The participants were divided into two age groups: the three youngest age cohorts (3 - 9 years at the baseline and 6 - 12 years at the follow-up) were combined as a children’s group. Similarly, the three oldest age cohorts (12 - 18 years at the baseline and 15 - 21 years at the follow-up) were combined as an adolescent’s group.
New apoE genotyping was conducted by analyzing two SNPs (rs429358 and rs7412). Genomic DNA was extracted from peripheral blood leukocytes by using the QIAampÒDNA Blood Minikit and automated biorobot M48 extraction (Qiagen, Hilden, Germany). Genotyping was performed by using TaqmanÒSNP Genotyping Assays (rs429358 assay C 3084793_20; rs7412 assay C_904973_10) and the ABI Prism 7900HT Sequence Detection System (Applied Biosystems, Foster City, CA, USA). Discrepancies did not emerge in the genotyping results of duplicate samples. The old method for genotyping apoE was based on isoelectric focusing, cysteamine treatment and immunoblotting from delipidated plasma and has been documented in detail elsewhere [
The same methods in assessing temperament were used as in our original study [
Second, in 1983 mothers also assessed their children’s temperament with the semantic differential measure that was based on the Operation Family Study [
In addition to mother-ratings, self-ratings on temperament were also made in 1983 by adolescent participants (aged 15 - 21) with the semantic differential measure. The scales mental vitality, sociability and positive emotionality were calculated similarly as described above. Reliabilities (Cronbach’s alphas) in the present sample for self-rated temperament were 0.48 for mental vitality, 0.54 for sociability and 0.38 for positive emotionality.
Analyses were conducted separately for children and adolescents. The analysis of covariance was carried out between five genotype groups of apoE and each temperament dimension separately. First, all possible sex × apoE interactions predicting temperament were tested. As all interactions were non-significant, sexes were analyzed together with sex as a covariate.
The means of the temperament dimensions of motor activity, cooperativeness and negative emotionality did not differ between the apoE groups. All associations were nonsignificant at the baseline and at the follow-up among both children and adolescents (all p-values > 0.10). This replicates our original results on absence of association of apoE with cooperativeness, negative emotionality and adolescents’ motor activity. The original significant finding (p < 0.05) of children’s motor activity did not replicate, as children’s motor activity was now unrelated to the apoE polymorphisms (p = 0.145).