Promoting Healthy Lifestyles with Personalized, APOE Genotype Based Health Information: The Effects on Psychological-, Health Behavioral and Clinical Factors

There is an increasing demand for individualized, genotype-based health advice. The general population-based dietary recommendations do not always motivate people to change their life-style, and partly following this, cardiovascular diseases (CVD) are a major cause of death in worldwide. Using genotype-based nutrition and health information (e.g. nutrigenetics) in health education is a relatively new approach, although genetic variation is known to cause individual differences in response to dietary factors. Response to changes in dietary fat quality varies, for example, among different APOE genotypes. Research in this field is challenging, because several non-modifiable (genetic, age, sex) and modifiable (e.g. lifestyle, dietary, physical activity) factors together and with interaction affect the risk of life-style related diseases (e.g. CVD). The other challenge is the psychological factors (e.g. anxiety, threat, stress, motivation, attitude), which also have an effect on health behavior. The genotype-based information is always a very sensitive topic, because it can also cause some negative consequences and feelings (e.g. depression, increased anxiety). The aim of this series of studies was firstly to study how individual, genotype-based health information affects an individual’s health form three aspects, and secondly whether this could be one method in the future to prevent lifestyle-related diseases, such as CVD. The first study concentrated on the psychological effects; the focus of the second study was on health behavior effects, and the third study concentrated on clinical effects. In the fourth study of this series, the focus was on all these three aspects and their associations with each other. The genetic risk and health information was the APOE gene and its effects on CVD. To study the effect of APOE genotype-based health information in prevention of CVD, a total of 151 volunteers attended the baseline assessments (T0), of which 122 healthy adults (aged 20 – 67 y) passed the inclusion criteria and started the one-year intervention. The participants (n = 122) were randomized into a control group (n = 61) and an intervention group (n = 61). There were 21 participants in the intervention Ɛ4+ group (including APOE genotypes 3/4 and 4/4) and 40 participants in the intervention Ɛ4- group (including APOE genotypes 2/3 and 3/3). The control group included 61 participants (including APOE genotypes 3/4, 4/4, 2/3, 3/3 and 2/2). The baseline (T0) and follow-up assessments (T1, T2, T3) included detailed measurements of psychological (threat and anxiety experience, stage of change), and behavioral (dietary fat quality, consumption of vegetables, - high fat/sugar foods and –alcohol, physical activity and health and taste attitudes) and clinical factors (total-, LDL- HDL cholesterol, triglycerides, blood pressure, blood glucose (0h and 2h), body mass index, waist circumference and body fat percentage). During the intervention six different communication sessions (lectures on healthy lifestyle and nutrigenomics, health messages by mail, and personal discussion with the doctor) were arranged. The intervention groups (Ɛ4+ and Ɛ4-) received their APOE genotype information and health message at the beginning of the intervention. The control group received their APOE genotype information after the intervention. For the analyses in this dissertation, the results for 106/107 participants were analyzed. In the intervention, there were 16 participants in the high-risk (Ɛ4+) group and 35 in the low-risk (Ɛ4-) group. The control group had 55 participants in studies III-IV and 56 participants in studies I-II. The intervention had both short-term (≤ 6 months) and long-term (12 months) effects on health behavior and clinical factors. The short-term effects were found in dietary fat quality and waist circumference. Dietary fat quality improved more in the Ɛ4+ group than the Ɛ4- and the control groups as the personal, genotype-based health information and waist circumference lowered more in the Ɛ4+ group compared with the control group. Both these changes differed significantly between the Ɛ4+ and control groups (p<0.05). A long-term effect was found in triglyceride values (p<0.05), which lowered more in Ɛ4+ compared with the control group during the intervention. Short-term effects were also found in the threat experience, which increased mostly in the Ɛ4+ group after the genetic feedback (p<0.05), but it decreased after 12 months, although remaining at a higher level compared to the baseline (T0). In addition, Study IV found that changes in the psychological factors (anxiety and threat experience, motivation), health and taste attitudes, and health behaviors (dietary, alcohol consumption, and physical activity) did not directly explain the changes in triglyceride values and waist circumference. However, change caused by a threat experience may have affected the change in triglycerides through total- and HDL cholesterol. In conclusion, this dissertation study has given some indications that individual, genotypebased health information could be one potential option in the future to prevent lifestyle-related diseases in public health care. The results of this study imply that personal genetic information, based on APOE, may have positive effects on dietary fat quality and some cardiovascular risk markers (e.g., improvement in triglyceride values and waist circumference). This study also suggests that psychological factors (e.g. anxiety and threat experience) may not be an obstacle for healthy people to use genotype-based health information to promote healthy lifestyles. However, even in the case of very personal health information, in order to achieve a permanent health behavior change, it is important to include attitudes and other psychological factors (e.g. motivation), as well as intensive repetition and a longer intervention duration. This research will serve as a basis for future studies and its information can be used to develop targeted interventions, including health information based on genotyping that would aim at preventing lifestyle diseases. People’s interest in personalized health advices has increased, while also the costs of genetic screening have decreased. Therefore, generally speaking, it can be assumed that genetic screening as a part of the prevention of lifestyle-related diseases may become more common in the future. In consequence, more research is required about how to make genetic screening a practical tool in public health care, and how to efficiently achieve long-term changes.

Evaluation of the main energy scenarios for the global energy transition

Energy scenarios are used as a tool to examine credible future states and pathways. The one who constructs a scenario defines the framework in which the possible outcomes exist. The credibility of a scenario depends on its compatibility with real world experiences, and on how well the general information of the study, methodology, and originality and processing of data are disclosed. In the thesis, selected global energy scenarios’ transparency and desirability from the society’s point of view were evaluated based on literature derived criteria. The global energy transition consists of changes to social conventions and economic development in addition to technological development. Energy solutions are economic and ethical choices due to far-reaching impacts of energy decision-making. Currently the global energy system is mostly based on fossil fuels, which is unsustainable over the long-term due to various reasons: negative climate change impacts, negative health impacts, depletion of fossil fuel reserves, resource-use conflicts with water management and food supply, loss of biodiversity, challenge to preserve ecosystems and resources for future generations, and inability of fossil fuels to provide universal access to modern energy services. Nuclear power and carbon capture and storage cannot be regarded as sustainable energy solutions due to their inherent risks and required long-term storage. The energy transition is driven by a growing energy demand, decreasing costs of renewables, modularity and scalability of renewable technologies, macroeconomic benefits of using renewables, investors’ risk awareness, renewable energy related attractive business opportunities, almost even distribution of solar and wind resources on the planet, growing awareness of the planet’s environmental status, environmental movements and tougher environmental legislation. Many of the investigated scenarios identified solar and wind power as a backbone for future energy systems. The scenarios, in which the solar and wind potentials were deployed in largest scale, met best the set out sustainability criteria. In future research, energy scenarios’ transparency can be improved by better disclosure on who has ordered the study, clarifying the funding, clearly referencing to used sources and indicating processed data, and by exploring how variations in cost assumptions and deployment of technologies influence on the outcomes of the study.

Suunnatun evoluution menetelmät sekä Rekombinanttivasta-aineen affiniteetin parantaminen suunnatun evoluution avulla.

Erilaisilla mutageneesimenetelmillä pyritään muokkaamaan geneettistä koodia ja luomaan tätä kautta kestävämpiä ja sitomiskyvyltään parempia proteiineja. Ensimmäiset geneettiset mutaatiot olivat poikkeuksetta satunnaisia, jotka tapahtuivat ennalta määräämättömiin kohtiin DNA-sekvenssiä. Tänä päivänä on mahdollista tehdä suunnatun evoluution keinoin tarkoin suunniteltuja tai satunnaisia paikkakohtaisia mutaatioita. Yhdestä kohdegeenistä on mahdollista muodostaa lukemattomia eri variantteja jolloin ongelman muodostaa näiden muokattujen varianttien eristäminen lukemattomien yksilöiden joukosta. Suunnatun evoluution menetelmissä tuotetaan muokattuja proteiineja, jotka omaavat kehittyneitä ominaisuuksia ja sallimalla vain tämän ominaisuuden omaavien yksilöiden lisääntyä. Muokattuja proteiineja seulotaan sekä in vivo - että in vitro -pohjaisilla näyttötekniikoilla, sillä kunkin menetelmän käyttö riippuu seulottavasta molekyylistä. Uusia näyttötekniikoita kehitetään jatkuvasti korjaamaan ja kehittämään edellisissä olevia heikkouksia. Työssä pyrittiin parantamaan synteettisestä vasta-ainekirjastosta eristetyn HRPII-spesifisen Fab-vasta-ainefragmentin affiniteettia suunnatun evoluution avulla. Vasta-ainegeenin hypervariaabelialueisiin tehtiin paikkakohtaisia satunnaisia mutaatioita kahdella eri strategialla: kohdennetulla alukepohjaisella PCR-mutageneesillä ja selektiivisellä RCA-mutageneesillä. Lisäksi kahdella eri strategialla muokatuista sitojista muodostettiin rekombinaatioklooneja yhdistämällä näiden kevyen ketjun hypervariaabelialueita L1 ja L3 keskenään. Mutatoiduista vasta-ainefragmenttigeeneistä valmistettiin geenikirjastot, jotka rikastettiin faaginäyttötekniikalla. Kirjastoista eristettyjen sitojien affiniteetti mitattiin biokerrosinterferometrian avulla ja lämpökestävyys differentiaali pyyhkäisykalorimetrian avulla. Mutageneesimenetelmillä tuotetut kirjastot sisälsivät suunnitelman mukaisia mutaatioita ja tavoitellut kullekin kirjastolle asetetut teoreettiset diversiteetit. Kirjastoista eristettyjen ja rekombinaation avulla muokatun Fab-vasta-ainefragmentin sitoutumisvoimakkuus oli biokerrosinterferometrialla mitattuna 116-kertaisesti parempi alkuperäiseen vasta-ainefragmenttiin verratuna. Rekombinaatiokloonin assosiaatio- ja dissosiaatiovakiot paranivat oleellisesti templaattina toimineeseen alkuperäiseen vasta-ainefragmenttiin nähden. Affiniteettiparannuksen lisäksi myös mutantin sulamislämpötila oli yli 1 °C asteen korkeampi kuin alkuperäisen vasta-ainefragmentin. Kohonneen affiniteetin lisäksi klooni rekombinaatioiden yhteydessä havaittiin myös laskua sitoutumisvoimakkuudessa suhteessa rekombinaatiokloonin muodostamiin CDR-L1 - ja -L3 -osiin.

Common dyslipidemias, high lipoprotein(a) concentrations and endothelial function in the children of the STRIP study families

Extreme lipid values predisposing on illnesses are dyslipidemias. Dyslipidemias evolve in early childhood, but their significance or persistency is not well known. Common dyslipidemias may aggregate in the same families. This thesis is a part of the longitudinal randomized Special Turku coronary Risk factor Intervention Project STRIP, in which 1054 families with six months old children were randomized to a control or to an intervention group. The family lipid data from the first 11 years was used. Fasting samples at the age of five years defined the lipid phenotypes. The dyslipidemias coexisting in the parent and the child were studied. At the age of 11 years 402 children participated artery ultrasound studies. The significance of the childhood dyslipidemias and lipoprotein(a) concentration on endothelial function was evaluated with the flow mediated arterial dilatation test. Frequently elevated non-HDL cholesterol concentration from one to seven-year-old children associated to similar parental dyslipidemia that improved the predictive value of the childhood sample. The familial combinations were hypercholesterolemia (2.3%), hypertriglyceridemia (2.0%), familial combined hyperlipidemia (1.8%), and isolated low HDL-cholesterol concentration (1.4%). Combined hyperlipidemia in a parent predicted most frequently the child’s hyperlipidemia. High lipoprotein(a) concentration aggregated in some families and associated to childhood attenuated brachial artery dilatation. Hypercholesterolemia and high lipoprotein(a) concentration at five years of age predicted attenuated dilatation. This study demonstrated that parental dyslipidemias and high lipoprotein(a) concentration help to find early childhood dyslipidemias. The association of hypercholesterolemia and lipoprotein(a) concentration with endothelial function emphasizes the importance of the early recognition of the dyslipidemias.