Genomische Bearbeitung und Auswahl auf der Grundlage von Genen, die mit sportlichen Leistungen in Verbindung stehen – einige bioethische Fragen

Projekt ljudskoga genoma završen je 2003. godine, a njegovi su rezultati otkrili dotada nepoznate detalje o našem genomu: skupinu informacija o tome kako ljudska bića izgledaju, kako djeluju, osjećaju, misle i razvijaju se. Uskoro su ostvarene i druge međunarodne suradnje poput projekta HapMap i Projekta 1000 genoma. Unatoč tomu što su primarno bili usmjereni na istraživanje varijabilnosti u ljudskoj populaciji, kao i moguće povezanosti različitih varijacija s različitim stanjima i bolestima, ti su projekti također znatno utjecali na razumijevanje utjecaja gena na sportski uspjeh. Usporedno su razvijene poboljšane metode genske analize i genskoga preinačavanja na temelju kojih je postalo moguće utvrditi kandidatske gene odgovorne za različite fenotipe uspješnosti u sportu te razviti protokole slične genskim terapijama za poboljšanje sportskih natjecateljskih performansi sportaša. Ovaj rad daje pregled razvoja u genetici, pregled kandidatskih gena povezanih sa sportskim natjecateljskim performansama te etičke dvojbe vezane uz preinačavanje genoma radi poboljšavanja sportskih natjecateljskih performansi.In 2003 the final results of the Human Genome Project revealed the details of our genome: a set of information about how human beings look, how we act, feel, think and develop. Soon after, other global collaborations such as the HapMap project and 1000 Genomes Project were conducted. Although the main focus was to investigate the variability in human populations and the possible connections of certain variations to different conditions and diseases, these projects also had a great impact on the understanding of the genetic influence on sports performance. In parallel, improved methods for gene analysis and gene editing were developed. Based on those methods, it became possible to detect candidate genes responsible for different performance phenotypes and develop protocols similar to gene therapies for performance enhancement in athletes. This review covers developments in genetics, the overview of candidate genes associated with athletic performance, and ethical dilemmas related to the modification of genome for sport performance enhancement.En 2003, les résultats finaux du Projet génome humain ont révélé les détails sur la structure de notre génome : un ensemble d’informations sur l’apparence physique de l’être humain, sur sa manière d’agir, de sentir, de penser, et de se développer. Peu de temps après, d’autres collaborations mondiales telles que le projet HapMap et le projet 1000 Genomes ont été menées à terme. Axés essentiellement sur la variabilité de la population humaine et sur les possibles liens de certaines variations avec différents états et maladies, ces projets ont toutefois eu un important impact sur notre manière de comprendre l’influence que les gènes exercent sur la performance sportive. En parallèle, des méthodes améliorées pour l’analyse du gène et la modification du gène ont été développées. Il est devenu possible sur la base de ces méthodes de détecter les gènes candidats responsables des différents phénotypes associés à la performance et de développer des protocoles similaires aux thérapies géniques afin d’améliorer les performances chez les athlètes. Cet article passe en revue les développements en génétique, donne un aperçu général des gènes candidats associés à la performance athlétique et des dilemmes éthiques liés à la modification du génome dans le but d’améliorer la performance sportive.Im Jahr 2003 enthüllten die endgültigen Ergebnisse des Humangenomprojekts die Details unseres Genoms: Eine Reihe von Informationen darüber, wie Menschen aussehen, wie wir handeln, fühlen, denken und uns entwickeln. Bald darauf wurden weitere weltweite Kooperationen wie das HapMap-Projekt und das 1000-Genome-Projekt in die Tat umgesetzt. Obgleich das Hauptaugenmerk auf der Variabilität der menschlichen Population und den möglichen Verquickungen bestimmter Variationen mit verschiedenen Zuständen und Krankheiten lag, übten diese Projekte auch eine große Wirkung auf das Verständnis des genetischen Einflusses auf die sportliche Leistung aus. Parallel dazu wurden verbesserte Methoden zur Genanalyse und Genbearbeitung entwickelt. Basierend auf diesen Methoden wurde es machbar, Kandidatengene zu detektieren, die für verschiedene Leistungsphänotypen verantwortlich sind, und Protokolle zu entwickeln, die Gentherapien zur Leistungssteigerung bei Sportlern ähneln. Dieser Aufsatz behandelt Entwicklungen in der Genetik, den Überblick über Kandidatengene im Zusammenhang mit sportlicher Leistung und ethische Dilemmata bezüglich der Modifizierung des Genoms zur Steigerung der sportlichen Leistung

Are the Physically Active Adolescents Belonging to the »At Risk of Overweight« BMI Category Really Fat?

The adolescence is recognized as one of the critical periods for the development of obesity. Children and adolescents who practice sports regularly have higher muscle mass and lower percentage of body fat than their peers who are physically less active. Since body mass index (BMI) is a widely used indicator of overweight/obesity in spite of the fact that it directly measures excess in weight but not in fat, it often misclassifies athletic populations, both children and adults. The specific aim of this study was to evaluate whether BMI adequately assesses fatness in adolescents, especially physically active ones. The analysis was performed on anthropometric data from two surveys (1997 and 2009/2010) of Zagreb secondary school adolescents, 1315 girls and 1034 boys, aged 15–19 years. The group defined as »physically active« consisted of adolescents who practice organized sports (36.2% girls, 44.6% boys), while the »physically inactive« group was made of their peers who practice sport only as a part of physical education in schools. The standardized values, calculated within each sex by survey, were used for comparison of adolescents with different levels of physical activity. Physically active adolescents of both sexes had lower sum of skinfolds mean Z-values (pgirls<0.05, pboys<0.001); additionally, boys had higher Z-values for body weight (p<0.05) and triceps/subscapular ratio (indicating peripheral distribution of body fat) (p<0.05) than their less active peers. In order to evaluate whether BMI was adequate indicator for body composition during adolescence, we estimated the concordance of above-median category defined by BMI and the other body fat indicators. The largest discrepancy was found for sum of skinfolds in both sexes and was more pronounced in physically active adolescents. This finding was further confirmed in more extreme BMI category (85th – 95th percentile) which indicated that adolescents categorized as »at risk of overweight« were predominantly characterized by larger lean body mass and not by increased fatness

Anthropometric indices of nutritional status in Croatian oldest old: new equations to predict height and weight

Anthropometry is an essential tool in the geriatric nutritional assessment. Measuring height and weight can be quite problematic in the old age so they can be estimated using theWHO equations. The purpose of this study was to: (a) show anthropometric indices of nutritional status of the ambulatory institutionalized oldest old in Zagreb, Croatia; (b) examine the adequacy of WHO equations for predicting height and weight of oldest old persons; (c) develop population-specific equations for estimating height and weight. The sample of this cross-sectional study comprised 314 examinees (F/M=234/80, 85-101 years). The classic anthropometric parameters (height, weight, extremities\u27 circumferences, knee height and skinfolds) were measured. The adequacy of WHO equations for predicting height and weight in Croatian oldest old was assessed using the paired t-test. Multiple linear regression analysis was performed to derive population-specific equations for predicting height and weight. The sexual dimorphismwas found in several anthropometric indices;men were taller, had larger weight and knee height, while women had larger triceps skinfold thickness. In women, most indices declined with age and in men the negative relation of knee height with age indicated a secular trend. The WHO equations for elderly acceptably predicted nothing but height in oldest old women. The presently developed equations, using the sameWHO\u27s predictor variables, proved to be more adequate for the studied population. The equations developed for estimating height and weight of non-ambulatory oldest old Croatians proved to be more appropriate than WHO equations and are therefore proposed for use in the everyday practice

Maternal Physical Activity in Pregnancy and Newborns` Anthropometry-The Preface From the CRIBS Study

Health benefits of physical activity during pregnancy include reduced risk of excessive gestational weight gain and conditions such as gestational diabetes, preeclampsia and preterm birth. The ongoing CRoatian Islands Birth Cohort Study (CRIBS) is the first cohort study in the South-Eastern Europe with an aim to assess the prevalence of risk factors (biological, environmental and behavioral) for the Metabolic Syndrome in populations from Dalmatian islands of Hvar and Brač and coastal Split city with its surroundings. At the time of writing, Over 350 pregnant women and 220 of their newborns have been involved in the study. Here we present the preliminary results of testing the association of mothers` self-estimated physical activity during pregnancy with newborns` anthropometric characteristics (birth weight, length and head circumference) using the data from questionnaires and obstetric records of 116 mother – newborn pairs. The difference in weight-at-birth was detected between newborn girls whose mothers were from Low vs. Intensive physical activity categories, as well as from Moderate vs. Intensive physical activity categories. In addition to that, the significant difference in weight-at-birth and height/length-at-birth was detected between newborn boys whose mothers were from Moderate vs. Intensive physical activity categories (p<0.01). No association between self-estimated level of physical activity and mothers’ body mass index was found. For women with normal pregnancies, light occupational activities do not cause problems with the fetal growth rate, but the same was not reported for women who maintained high-intensity activities

Maternal Physical Activity in Pregnancy and Newborns` Anthropometry-The Preface From the CRIBS Study

Health benefits of physical activity during pregnancy include reduced risk of excessive gestational weight gain and conditions such as gestational diabetes, preeclampsia and preterm birth. The ongoing CRoatian Islands Birth Cohort Study (CRIBS) is the first cohort study in the South-Eastern Europe with an aim to assess the prevalence of risk factors (biological, environmental and behavioral) for the Metabolic Syndrome in populations from Dalmatian islands of Hvar and Brač and coastal Split city with its surroundings. At the time of writing, Over 350 pregnant women and 220 of their newborns have been involved in the study. Here we present the preliminary results of testing the association of mothers` self-estimated physical activity during pregnancy with newborns` anthropometric characteristics (birth weight, length and head circumference) using the data from questionnaires and obstetric records of 116 mother – newborn pairs. The difference in weight-at-birth was detected between newborn girls whose mothers were from Low vs. Intensive physical activity categories, as well as from Moderate vs. Intensive physical activity categories. In addition to that, the significant difference in weight-at-birth and height/length-at-birth was detected between newborn boys whose mothers were from Moderate vs. Intensive physical activity categories (p<0.01). No association between self-estimated level of physical activity and mothers’ body mass index was found. For women with normal pregnancies, light occupational activities do not cause problems with the fetal growth rate, but the same was not reported for women who maintained high-intensity activities

A sociodemographic profile of the participants in the Croatian Islands\u27 Birth Cohort Study (CRIBS)

U radu je predstavljen sociodemografski profil sudionica u Kohortnoj studiji rođenih na istočnojadranskim otocima (CRIBS), prvoj longitudinalnoj studiji u Hrvatskoj koja prati trudnice i njihovu djecu do navršene dvije godine života. Uzorak čini 286 trudnica (145 s otoka Brača i Hvara te 141 trudnica s kopna). Cilj je ove studije: 1) opisati glavna obilježja CRIBS uzorka, 2) usporediti uzorak s općom hrvatskom populacijom, 3) analizirati razlike među sudionicama u projektu CRIBS s obzirom na mjesto stanovanja (otoci vs. kopno) i tip obitelji u kojoj žive (nuklearna vs. proširena obitelj). U usporedbi s ženama s kopna otočanke su češće višerotkinje i češće završavaju samo srednju školu, dok većina žena na kopnu ima fakultetsko obrazovanje. Prevladavanje različitih tipova obitelji značajno se razlikuje između otoka i kopna, otočanke žive u proširenim obiteljima i imaju niže prosječne prihode kućanstava.This paper presents the socio-demographic profile of participants in the Croatian Islands\u27 Birth Cohort Study (CRIBS), the first longitudinal study in Croatia to follow pregnant women and their children up to the age of two. The sample consisted of 286 pregnant women (145 from the islands of Brač and Hvar, and 141 from the mainland). The study aimed to: 1) summarise the main characteristics of the CRIBS study sample; 2) compare the sample with the general population of Croatia; 3) analyse the differences between the CRIBS participants according to place of residence (islands vs. mainland) and family type (nuclear vs. extended family). In comparison with women from the mainland, islander women had more often given birth to more than one child and finished only secondary school, while most of the women from the mainland had university degree. The prevalence of different family types also significantly differed between the islands and mainland, with islanders living in extended families and having lower average household income

Pharmacogenetic distinction of the Croatian population from the European average

Aim To compare the Croatian and European population in terms of allele frequencies of clinically relevant polymorphisms in drug absorption, distribution, metabolism, and excretion (ADME) genes. Methods In 429 Croatian participants, we genotyped 27 loci in 20 ADME genes. The obtained frequencies were merged with the published frequencies for the Croatian population by sample size weighting. The study sample obtained in this way was compared with the average data for the European population from the gnomAD database. Results Variant allele frequencies in the Croatian population were higher in three and lower in two polymorphisms (Benjamini-Hochberg-corrected P values: 0.0027 for CYP2B6*4 rs2279343, CYP2C9*2 rs1799853, and VKORC1 rs9923231; 0.0297 for GSTP1 rs1695; 0.0455 for CYP2A6 rs1801272) compared with the European population. The most marked difference was observed for CYP2B6*4 (9.3% in Europe vs 24.3% in Croatia). The most clinically relevant findings were higher variant allele frequencies in two polymorphisms related to lower warfarin requirements: VKORC1*2 (34.9% in Europe vs 40.1% in Croatia) and CYP2C9*2 (12.3% in Europe vs 14.7% in Croatia). This indicates that three-quarters of Croatian people have at least one variant allele at these loci. Variants in genes GSTP1 and CYP2A6 were significantly less frequently observed in Croatia. Conclusions Croatian population has a higher bleeding and over-anticoagulation risk, which is why we recommend the prescription of lower doses of anticoagulation drugs such as warfarin and acenocoumarol. Lower phenytoin, and higher bupropion and efavirenz doses are also recommended in the Croatian population

Mediterranean Diet in Pregnancy and its Association with Newborns` Body Size in Dalmatia, Croatia – The Preliminary Results of the Croatian Islands Birth Cohort Study

A pregnant woman’s nutrition has an impact on her offspring’s birth size. Although health benefits of Mediterranean diet are widely confirmed, the poor compliance with its recommendations has been detected in the population of Dalmatia, coastal region of Croatia. Data from 122 mother–newborn pairs, participants in the ongoing Croatian Islands` Birth Cohort Study (CRIBS), were analyzed: (1) to test whether pregnant women in the study consume Mediterranean diet that is traditional in this area, and (2) to examine the association of maternal diet in pregnancy with newborns` birth weight, length and head circumference. The preliminary results of the factor analysis of 20 items from Food Frequency Questionnaire (FFQ) resulted in two significant factors, both having positive loading with the components of Mediterranean diet. Factor 1 had highest positive loadings for blue fish, white fish, olive oil and fatty cheese consumption consistent with the Mediterranean diet and Factor 2 had highest loading coefficients for fermented milk products (yogurt), sea food, cereals and legumes. Linear regression analyses resulted in model for weight at birth (R2=0.071, p<0.05) which included as predictors living location (island or mainland) and FFQ Factor 2, which was also, in combination with moderate physical activity, predictive for newborns with z-scored weight at birth values above 15% of the lowest values in the logistic regression model. Pregnant women from the CRIBS study mostly follow Mediterranean diet but its association with weight at birth, although found in this research, has to be confirmed on a bigger sample

Impact of pre-pregnancy BMI on blood glucose levels in pregnancy and on the anthropometry of newborns – preliminary insights from the Croatian Islands\u27 Birth Cohort Study (CRIBS)

The aim of this study was to investigate the relationship between pre-pregnancy body mass index (BMI) and fasting blood glucose level in pregnancy on the anthropometry of newborns. The sample consisted of 171 healthy pregnant women and their newborns from the Croatian Islands\u27 Birth Cohort Study. Peripheral blood of pregnant women was taken in the second trimester and fasting glucose values >5.1 mmol/l were considered elevated. Anthropometric variables (body weight, height and waist circumference) were measured according to the International Biological Program. Pre-pregnancy BMI and fasting glucose levels during pregnancy were significantly positively correlated (p<0,01), as were pre-pregnancy BMI and birth weight (p<0,05), length (p<0,01), and head circumference (p<0,05) of the newborns. Hyperglycaemic women gave birth to significantly heavier newborn girls then normal glycaemic women (p<0.05). In conclusion, there was a positive correlation between pre-pregnancy BMI, fasting glucose during pregnancy and the anthropometry of newborns in this study

Mediterranean Diet in Pregnancy and its Association with Newborns` Body Size in Dalmatia, Croatia – The Preliminary Results of the Croatian Islands Birth Cohort Study

A pregnant woman’s nutrition has an impact on her offspring’s birth size. Although health benefits of Mediterranean diet are widely confirmed, the poor compliance with its recommendations has been detected in the population of Dalmatia, coastal region of Croatia. Data from 122 mother–newborn pairs, participants in the ongoing Croatian Islands` Birth Cohort Study (CRIBS), were analyzed: (1) to test whether pregnant women in the study consume Mediterranean diet that is traditional in this area, and (2) to examine the association of maternal diet in pregnancy with newborns` birth weight, length and head circumference. The preliminary results of the factor analysis of 20 items from Food Frequency Questionnaire (FFQ) resulted in two significant factors, both having positive loading with the components of Mediterranean diet. Factor 1 had highest positive loadings for blue fish, white fish, olive oil and fatty cheese consumption consistent with the Mediterranean diet and Factor 2 had highest loading coefficients for fermented milk products (yogurt), sea food, cereals and legumes. Linear regression analyses resulted in model for weight at birth (R2=0.071, p<0.05) which included as predictors living location (island or mainland) and FFQ Factor 2, which was also, in combination with moderate physical activity, predictive for newborns with z-scored weight at birth values above 15% of the lowest values in the logistic regression model. Pregnant women from the CRIBS study mostly follow Mediterranean diet but its association with weight at birth, although found in this research, has to be confirmed on a bigger sample