Linking infant size and early growth with maternal lifestyle and breastfeeding - the first year of life in the CRIBS cohort.

BACKGROUND: Every third child in Croatia is classed as overweight or obese. Infant growth can represent early warning signs for obesity. AIM: To detect early risk factors for obesity by investigating infant size and early growth trajectories and their association with maternal lifestyle and breastfeeding. SUBJECTS AND METHODS: Ninety-eight mother-child pairs from the Croatian Islands' Birth Cohort Study (CRIBS) cohort were included in the study. Data were collected from questionnaires and medical records. Growth data were converted to Z-scores using World Health Organisation (WHO) standards and used as the primary outcome. RESULTS: Z-score trajectories in the first year of life were in line with WHO standards. A direct link between infant size and maternal socioeconomic status (SES) or breastfeeding was not detected. However, child weight gain in the first 6 months was associated with maternal body mass index (BMI) before pregnancy (p < 0.01). A positive association was also established between breastfeeding and maternal SES and mothers that report an unhealthy diet have heavier children (p < 0.05, respectively). CONCLUSION: Infant size and early growth in Croatia is in line with WHO standards and risk factors for obesity development were detectable in the first year of life, but not highly pronounced. However, more effective BMI monitoring and promotion of a healthy diet and lifestyle of women before and during pregnancy is needed.

Testing the Institute of Medicine (IOM) recommendations on maternal reproductive health and associated neonatal characteristics in a transitional, Mediterranean population.

BACKGROUND: High pre-pregnancy body mass index (BMI) and excessive gestational weight gain (GWG) are significant risk factors for maternal and neonatal health. AIM: To assess pre-pregnancy BMI and GWG during pregnancy and their association with different maternal and neonatal characteristics in the transitional Mediterranean population from the Eastern Adriatic islands. SUBJECTS AND METHODS: Two hundred and sixty-two mother-child dyads from the CRoatian Islands' Birth Cohort Study (CRIBS) were included in the study. Chi-square test, ANOVA, and regression analysis were used to test the association between selected characteristics. RESULTS: In total, 22% of women entered pregnancy as overweight/obese and 46.6% had excessive GWG. Pre-pregnancy overweight and obesity were significantly associated with elevated triglycerides uric acid levels, and decreased HDL cholesterol in pregnancy. Excessive GWG was associated with elevated fibrinogen and lipoprotein A levels. Women with high pre-pregnancy BMI and GWG values were more likely to give birth to babies that were large for gestational age (LGA), additionally confirmed in the multiple logistic regression model. CONCLUSION: High maternal pre-pregnancy BMI and excessive GWG were both significantly associated with deviated biochemical parameters and neonatal size. More careful monitoring of maternal nutritional status can lead to better pre- and perinatal maternal healthcare.

Croatian genetic heritage: an updated Y-chromosome story.

AIM: To analyze an additional set of ˝Y-chromosome genetic markers to acquire a more detailed insight into the diversity of the Croatian population. METHODS: A total of 518 Yfiler Plus profiles were genotyped. Allele frequencies, haplotype frequencies, and haplotype diversity were calculated by using the STRAF software v. 2.0.4. Genetic distances were quantified by Rst with AMOVA online tool from the YHRD. The evolutionary history was inferred with the neighbor-joining method of phylogenetic tree construction in the MEGAX software. Whit Athey's Haplogroup Predictor v. 5 was used for additional comparison with regional and other European populations. RESULTS: A total of 507 haplotypes were used for genetic STR analysis. An interpopulation study on 17 Y-STR markers showed the lowest genetic diversity between the Croatian and Bosnian-Herzegovinian populations and the highest between the Croatian and Irish populations. Additional interpopulation comparison with the original 27 Y-STR markers (for the population with available data) was also performed. A total of 518 haplotypes were used in the determination of haplogroup diversity. Haplogroup I with its sublineage I2a expressed the highest prevalence. The second most prevalent haplogroup was R, with its major sublineage R1a, except for the subpopulation of Hvar, where E1b1b was the second most prevalent haplogroup. Rare haplogroups also confirmed in this study were L, T, and Q. G1 was detected for the first time in the Croatian population. CONCLUSION: We obtained a new insight into the differences between examined subpopulations of Croatia and their possible (dis)similarities with neighboring and distant populations.

Stress, locus of control, hope and depression as determinants of quality of life of pregnant women: Croatian Islands' Birth Cohort Study (CRIBS).

The aims were to investigate determinants of the quality of life (QoL) of pregnant women. Total of 302 healthy women 18 to 28 weeks of gestation participated in prospective study. WHOQOL-bref, Multidimensional Health Locus of Control scales, Edinburgh Postnatal Depression Scale, and the perceived stress appraisals were administered. Various patterns of predictors for four domains of QoL were identified, for psychological (42% variance explained), social relationship (29%), environmental (29%) and physical health (25%). Depression and hope, together with the extent to which one's health is influenced by powerful other or chance should be targeted in health promotion strategies during pregnancy.

ANTHROPOMETRIC MEASUREMENTS, DIETARY HABITS, SERUM LIPID AND GLUCOSE LEVELS IN RELATION TO HIGH BLOOD PRESSURE AMONG ADOLESCENT BOYS AND GIRLS IN CROATIA.

The aim was to determine differences in anthropometric measurements, dietary habits, serum lipid and glucose levels in relation to high blood pressure (BP) among adolescent boys and girls in Croatia. The specific aim was to determine the effect of dietary habits and lifestyle on high BP in adolescents according to sex. The study included 260 (68.2%) adolescent girls and 121 (31.8%) boys with anthropometric data obtained (without missing values) from 246 girls and 111 boys. Participants answered questions from the questionnaire and anthropometric BP and blood test values were obtained. Non-parametric tests were used in analyses of reference intervals of systolic and diastolic BP in adolescent boys and girls according to age. High BP was defined as ≥90th percentile for adolescent girls and boys, with a value of ≥135/87.5 mm Hg. Mann-Whitney U test was used to analyze differences in anthropometric and laboratory values between the groups of girls and boys with high (≤90th percentile) and normal BP. Increase in systolic and diastolic BP was noted in the adolescents. In girls, BP values showed a decreasing systolic and increasing diastolic BP trend with age. Girls with high BP had a significantly higher body mass index (BMI) (p=0.020), waist circumference (WC) (p=0.002), waist-to-height ratio (WHtR) (p=0.016), waist-to-hip ratio (WHR) (p=0.043), hip circumference (HC) (p=0.015), triglyceride (TG) levels (p=0.021), higher prevalence of unhealthy diet at school breakfast (p=0.008) and lower prevalence of eating fish (p=0.02). Boys with high BP had a significantly higher BMI (p=0.045), WC (p=0.004), WHtR (p=0.017), WHR (p=0.022) and higher prevalence of eating meat products (p=0.015). Effective health interventions are needed to reduce the risk of developing cardiovascular diseases and preventing age-related illness.

Sex estimation of the sternum by automatic image processing of multi-slice computed tomography images in a Croatian population sample: a retrospective study.

AIM: To determine the sexual dimorphism of the sternum with standard measurements in a contemporary Croatian population sample using multi-slice computed tomography (MSCT) and to compare the data obtained by an automatic with those obtained by a manual approach. METHODS: Five sternal measurements were obtained from MSCT images of 73 men and 55 women and three sternal indices were calculated. Custom image analysis software was developed for automatic segmentation and calculation of sternal measurements. Measurements of sexual dimorphism were automatically calculated and compared with manual measurements. RESULTS: All of the sternal measurements exhibited significant differences between men and women. The discrepancies between manual and automatic measurements ranged from 2.8% to 3.6% of the mean average values obtained with the automatic approach. The most accurate single-variable discriminant function was sternal body length (82.8%), the most accurate index was sternal area (89.1%), and the discriminant function using three variables was manubrium width, sternal body length, and sternal body width (90.6%). CONCLUSION: Sternal measurements are a reliable sex indicator and can be used in forensic casework. Computer-aided measurement methods can accelerate sex estimation and improve its precision and accuracy.

Performance prediction models based on anthropometric, genetic and psychological traits of Croatian sprinters.

Elite athletes differ from each other in their characteristics according to their discipline. This study aimed to identify performance predictors in elite Croatian sprinters taking into consideration their anthropometric, psychological and genetic characteristics. One hundred and four elite Croatian sprinters (68 males and 36 females) participated in this study. Of them, 38 are currently competing in the 100-metre dash. The others are former sprinters. The participants underwent direct anthropometric assessment. Participants were also tested by means of the Competitive State Anxiety Inventory-2 and for ACE and ACTN3 polymorphisms. Multiple linear regression analysis was applied to identify the best model for performance prediction. Different models were developed for males and females. Anthropometric traits accounted for 44% of the variance in performance for males, 62% for females. Once other traits (psychological for females) were entered into the model, no additional contribution to the variance was observed. The most significant predictors of higher running velocity were bicristal diameter and foot dimensions in males, and leg length and clean one-repetition maximum in females. The findings suggest that performance in sprinters is associated with anthropometric characteristics, with biomechanical implications that may be used to provide a more complete evaluation of sprinters' performance.

Genetic heritage of Croatians in the Southeastern European gene pool-Y chromosome analysis of the Croatian continental and Island population.

OBJECTIVES: The research objective of this study is to enlarge and deepen the Y chromosome research on the Croatian population and enable additional insights into the population diversity and historic events that shaped the current genetic landscape of Croatia and Southeastern Europe (SEE). MATERIALS AND METHODS: A high-resolution phylogenetic and phylogeographic analysis of 66 biallelic (SNPs) and 17 microsatellite (STRs) markers of the Y chromosome was performed using 720 Croatian samples. The obtained results were placed in a wider European context by comparison with ∼4450 samples from a number of other European populations. RESULTS: A high diversity of haplogroups was observed in the overall Croatian sample, and all typical European Y chromosome haplogroups with corresponding clinal patterns were observed. Three distinct genetic signals were identifiable in the Croatian paternal gene pool - I2a1b-M423, R1a1a1b1a*-M558, and E1b1b1a1b1a-V13 haplogroups. DISCUSSION: The analyses of the dominant and autochthonous I2a1b-M423 lineage (>30%) suggest that SEE had a significant role in the Upper Paleolithic, the R1a1a1b1a*-M558 lineage (19%) represents a signal from present day Slavic populations of Central Europe in the Croatian population, and the phylogeography of the E1b1b1a1b1a-V13 clade (around 9%) implies cultural diffusion of agriculture into Europe via the Balkan Peninsula. Am. J. Hum. Biol., 2016. © 2016 Wiley Periodicals, Inc. Am. J. Hum. Biol. 28:837-845, 2016. © 2016Wiley Periodicals, Inc.

Diversity of Y-chromosomal and mtDNA Markers Included in Mediscope Chip within Two Albanian Subpopulations from Croatia and Kosovo: Preliminary Data.

The aim of this preliminary study is to analyze genetic specificity of Kosovo Albanians comparing with neighboring populations using new genetic tool - MEDISCOPE gene chip, to investigate the feasibility of this approach. We collected 37 DNA samples (9 Croats, 17 Albanians from Croatia and 11 Albanians from Kosovo) from unrelated males born in Croatia and Kosovo. Additionally, samples were expanded with female individuals and mtDNA analysis included a total of 61 samples (15 Croats, 23 Albanians from Croatia and 23 Albanians from Kosovo). This pilot study suggests that the usage of the MEDISCOPE chip could be recognized as an efficient tool within recognition of the population genetic specificity even within extremely small sample size.

Athletic Engagement and Athletic Identity in Top Croatian Sprint Runners.

The aim of the research was to determine construct validity and reliability for two questionnaires (Athlete Engagement Questionnaire-AEQ and Athletic Identity Measurement Scale-AIMS), applied on elite Croatian athletes-sprinters, as well as the correlations among the dimensions in these measuring instruments. Then, we have determined the differences in the dimensions of sport engagement and sport identity, according to gender, education level and winning medals on international competitions. A total of 71 elite athletes-sprinters (former and still active) are examined, from which 27 (38%) females and 44 (62%) males. The results of factor analyses revealed the existence of dimensions very similar as in the original instruments, which showed moderate to-high reliabilities. A small number of statistically significant correlations have been found between the dimensions of sport engagement and sport identity, mainly in male sprinter runners. Small number of statistically significant differences in the dimensions of sport engagement and sport identity have been found according to the gender, education level and winning medals on the international competitions. The most reasonable explanation of these differences could be given in terms of very similar characteristics of elite athletes on the same level of sport excellence.

Fish and Shellfish Intake and Diabetes in a Costal Population of the Adriatic.

The objective of the study was to examine the association between fish and shellfish intake and diabetes in an island population, and the design of the study was Cross-sectional. Two independent population-based field surveys were conducted in Hvar Island of the eastern Adriatic coast of Croatia in May 2007 and May 2008, with a total of 1,379 adult participants. In multivariable logistic regression models, total fish intake was positively associated with diabetes prevalence in the total population (OR(Q4 vs. Q1) = 1.64; 95% CI = 1.01-2.66; p-trend = 0.09). Oily fish intake also exhibited a positive association with diabetes prevalence in the total population (OR(Q4 vs. Q1) = 2.22; 95% CI = 1.35-3.64; p-trend = 0.01) and in analyses stratified by body mass index, males and those with a high waist circumference. The study suggests an association between oily fish intake and diabetes in the population of the Hvar Island in Croatia. Longitudinal studies incorporating measures of persistent organic pollutants and local cooking practices are warranted to identify factors in fatty fish that may influence the development or persistence of diabetes.

Maternal genetic heritage of Southeastern Europe reveals a new Croatian isolate and a novel, local sub-branching in the x2 haplogroup.

High mtDNA variation in Southeastern Europe (SEE) is a reflection of the turbulent and complex demographic history of this area, influenced by gene flow from various parts of Eurasia and a long history of intermixing. Our results of 1035 samples (488 from Croatia, 239 from Bosnia and 130 from Herzegovina, reported earlier, and 97 Slovenians and 81 individuals from Zumberak, reported here for the first time) show that the SEE maternal genetic diversity fits within a broader European maternal genetic landscape. The study also shows that the population of Zumberak, located in the continental part of Croatia, developed some unique mtDNA haplotypes and elevated haplogroup frequencies due to distinctive demographic history and can be considered a moderate genetic isolate. We also report seven samples from the Bosnian population and one Herzegovinian sample designated as X2* individuals that could not be assigned to any of its sublineages (X2a'o) according to the existing X2 phylogeny. In an attempt to clarify the phylogeny of our X2 samples, their mitochondrial DNA has been completely sequenced. We suppose that these lineages are signs of local microdifferentiation processes that occurred in the recent demographic past in this area and could possibly be marked as SEE-specific X2 sublineages.

Development and validation of a self-administered food frequency questionnaire to assess habitual dietary intake and quality of diet in healthy adults in the Republic of Croatia. .

Food frequency questionnaires (FFQ) are designed to assess habitual diet by asking about the frequency with which food items or specific food groups are consumed over a reference period. In this study, we have developed a FFQ to assess habitual dietary intake of healthy adults to estimate the quality of their nutrition and conducted a study to validate the developed FFQ against a three-day 24-hour recall. Second aim of the study is to establish the correlation between the FFQ to assess habitual dietary intake and a three-day 24-hour recall, in relation with participants' age and education level. FFQ used in our study was adapted from the Harvard Semiquantitative Food Frequency Questionnaire, consisted of 101 food items, divided into 9 groups. The 24-hour recalls were collected during one week (the same week when the FFQ was completed) and on each different day of the week (two weekdays and one weekend day). Both the FFQ and three day 24-hour recall were distributed to 100 healthy, employed subjects, 32 males (aged 39.73 +/- 14.02) and 36 females (aged 34.20 +/- 10.63). The results indicated that the developed FFQ is valid instrument to assess the habitual intake of energy and most of the nutrients in healthy adults in the Republic of Croatia, while men tended to have higher correlation coefficients than women and therefore a higher correlation of the FFQ with the three 24-hour recalls. Statistically significant correlations are not found between energy and nutrient intake based on the education level of the participants.

A comparison of two conative characteristics of top basketball and recreational table tennis players.

The purpose of this study is to adapt imported instruments for measuring multidimensional perfectionism in sport situations and perceived group cohesion, in terms of construct validity and reliability, as well as from the aspect of interpretability, addressed on Croatian samples of athletes. Group Environment Questionnaire (GEQ) and Sport Multidimensional Perfectionism Scale (MSSP) are applied. The sample of 223 male Croatian athletes comprises of N1 = 107 top basketball players from nine teams in A-1 Croatian Basketball League and N2 = 116 recreational table tennis players who play in Table Tennis Organization of Clubs and Actives in Zagreb. Principal Components Analyses at both instruments showed two-component structures: combined social-task cohesion and friendship were latent dimensions of perceived group cohesion, while the internalized standards and externalized standards revealed two aspects of multidimensional perfectionism in sport situations. In perceived group cohesion, basketball players achieved higher average results than table tennis players in the friendship, while the table tennis players showed higher combined social and task orientation than basketball players. In multidimensional sport perfectionism, basketball players have higher average result than table tennis players in the dimension of internalized perfectionism, but in externalized perfectionism there is no statistical significant difference. Younger players showed higher average results than older players in the dimension of friendship, while older players showed higher combined social and task orientation than younger players. Younger players have higher average scores in internalized perfectionism. The main importance of the research is adjustment of multidimensional perfectionism in sport situations and perceived group cohesion to Croatian athletes, providing additional possibility of cross-cultural adjustment of both concepts, psychometrically and theoretically.

Smoking habits according to metabolic traits in an island population of the eastern Adriatic Coast.

The study deals with the connection between metabolic syndrome (MS) and smoking habits of 1602 males and 828 females aged 18-97 years from the island of Hvar, Croatia. The age-adjusted prevalence of MS was higher in males (18.1-31.2%) than females (9.7-24.2%) by all five criteria that were defined, except the one by AHA/NHLBI. The overall prevalence of MS reached 12.9% by WHO using body mass index (BMI), 13.1% by EGIR, 14.5% by WHO using waist to hip ratio (WHR), 18.2% by NCEP/ATP III, 18.9% by AHA/NHLBI, and 26.7% by IDF criteria. The prevalence of smoking habits was similar in males (24.7%) and females (23.8%). The frequency of mild, moderate and heavy smoking was higher in males than females, 35.8:26.6%, 31.0:27.0%, and 35.9:7.7%, respectively. Age and sex had significant influence on BMI and WHR, both being highest in male former smokers (28.15 kg/m2 and 0.973, respectively) and in female non-smokers (27.18 kg/m2 and 0.869, respectively). The appearance of arterial hypertension (HTN) differed according to frequency of smoking; males had higher prevalence than females using WHO and EGIR criteria of blood pressure > or = 140/90 mmHg, even after age adjustment. In males and females respectively, systolic HTN in non-smokers was 20.7:15.1%, in former smokers 17.9:15.2% and in current smokers 16.9:13.0%; diastolic HTN in non-smokers was 19.8:12.7%, in former smokers 22.4:10.5%, and in current smokers 11.3:9.1%. By NCEP, AHA, IDF criteria of blood pressure > or = 130/85 mmHg, arterial HTN was also more prevalent in males than females; systolic HTN in non-smokers being 31.4:19.8%, in former smokers 29.9:12.7%, and in current smokers 25.4:11.1%; and diastolic HTN in non-smokers was 20.5:11.5%, in former smokers 24.8:11.3%, and in current smokers 14.7:9.4%. According to AHA/NHLBI and IDF criteria of high plasma glucose as > or = 5.6 mmoL/L, both males and females in all the three categories of smokers had glucose levels above the normal range (5.80-6.31 mmol/L in males and 5.80-5.91 mmol/L in females), except female current smokers (5.51 mmol/L). By WHO, EGIR and NCEP/ATP III criteria of high plasma glucose as > or = 6.1 mmol/L, only male non-smokers (6.31 mmol/L) and former smokers (6.24 mmol/L) had elevated levels. Considering normal HDL-cholesterol as > 1.0 mmol/L in males and > 1.2 mmol/L in females, both males and females in all the three smoker's categories had HDL within normal range; females having higher HDL levels (1.52 mmol/L) than males (1.30 mmol/L). Considering normal value for triglycerides as < 1.7 mmol/L, male former smokers (1.76 mmol/L) and current smokers (1.81 mmol/L) had higher levels; and as a whole group triglycerides were higher in males than females, 1.66:1.37 mmol/L respectively. The prevalence of MS differed between males and females using various MS criteria. Both males and females had the highest prevalence of MS by IDF criteria; male former smokers 60.5%, female non-smokers 51.4%, male non-smokers 53.8%, female former smokers 38.2%, and lowest in both male and female current smokers 39.8 and 33.0% respectively. In males, the lowest prevalence of MS was observed in non-smokers by AHA criteria (30.5%), in former smokers by WHO criteria (35.7%), and in current smokers using EGIR criteria (18.1%). Females in all the three smoker's categories had the lowest prevalence of MS using EGIR and WHO criteria. MS were less prevalent in current smokers than in non-smokers and former smokers.

Dietary patterns in adults from an Adriatic Island of Croatia and their associations with metabolic syndrome and its components.

Adriatic islanders have a high prevalence of metabolic syndrome (MetS) although they have traditionally practiced an active lifestyle and adhered to a Mediterranean diet. We performed a cross-sectional study to identify dietary patterns in a sample of 1442 adults from the island of Hvar, and determined whether MetS and its components: waist-circumference, serum triglycerides, fasting plasma glucose, HDL-cholesterol, and blood pressure, were related to an altered pattern of the traditional Mediterranean diet. Dietary intake was assessed by a food frequency questionnaire. MetS was defined using the International Diabetes Federation criteria. Our study showed that dietary patterns in this population have diversified from the traditional diet. Principal component analysis identified three major patterns. The meat, alcohol, and fish pattern (MAFp), sweets, grains, and fats pattern (SGFp), and an olive-oil, vegetables, and fruits pattern (OVFp) explained 30.6% of total dietary variance. The MAFp associated significantly with MetS (p = 0.027) and high plasma glucose (p = 0.006).

The Impact of Long-Term Clinoptilolite Administration on the Concentration Profile of Metals in Rodent Organisms.

Heavy metals are dangerous systemic toxicants that can induce multiple organ damage, primarily by inducing oxidative stress and mitochondrial damage. Clinoptilolite is a highly porous natural mineral with a magnificent capacity to eliminate metals from living organisms, mainly by ion-exchange and adsorption, thus providing detoxifying, antioxidant and anti-inflammatory medicinal effects. The in vivo efficiency and safety of the oral administration of clinoptilolite in its activated forms, tribomechanically activated zeolite (TMAZ) and Panaceo-Micro-Activated (PMA) zeolite, as well as the impact on the metallic biodistribution, was examined in healthy female rats. Concentration profiles of Al, As, Cd, Co, Pb, Ni and Sr were measured in rat blood, serum, femur, liver, kidney, small and large intestine, and brain using inductively coupled plasma mass spectrometry (ICP-MS) after a 12-week administration period. Our results point to a beneficial effect of clinoptilolite materials on the concentration profile of metals in female rats supplemented with the corresponding natural clinoptilolite materials, TMAZ and PMA zeolite. The observed decrease of measured toxicants in the kidney, femur, and small and large intestine after three months of oral intake occurred concomitantly with their most likely transient release into the bloodstream (serum) indicative of a detoxification process.

Refining the Global Phylogeny of Mitochondrial N1a, X, and HV2 Haplogroups Based on Rare Mitogenomes from Croatian Isolates.

Mitochondrial DNA (mtDNA) has been used for decades as a predominant tool in population genetics and as a valuable addition to forensic genetic research, owing to its unique maternal inheritance pattern that enables the tracing of individuals along the maternal lineage across numerous generations. The dynamic interplay between evolutionary forces, primarily genetic drift, bottlenecks, and the founder effect, can exert significant influence on genetic profiles. Consequently, the Adriatic islands have accumulated a subset of lineages that exhibits remarkable absence or rarity within other European populations. This distinctive genetic composition underscores the islands' potential as a significant resource in phylogenetic research, with implications reaching beyond regional boundaries to contribute to a global understanding. In the initial attempt to expand the mitochondrial forensic database of the Croatian population with haplotypes from small isolated communities, we sequenced mitogenomes of rare haplogroups from different Croatian island and mainland populations using next-generation sequencing (NGS). In the next step and based on the obtained results, we refined the global phylogeny of haplogroup N1a, HV2, and X by analyzing rare haplotypes, which are absent from the current phylogenetic tree. The trees were based on 16 novel and 52 previously published samples, revealing completely novel branches in the X and HV2 haplogroups and a new European cluster in the ancestral N1a variant, previously believed to be an exclusively African-Asian haplogroup. The research emphasizes the importance of investigating geographically isolated populations and their unique characteristics within a global context.

Genome-wide association of serum uric acid concentration: replication of sequence variants in an island population of the Adriatic coast of Croatia.

A genome-wide association study of serum uric acid (SUA) laevels was performed in a relatively isolated population of European descent from an island of the Adriatic coast of Croatia. The study sample included 532 unrelated and 768 related individuals from 235 pedigrees. Inflation due to relatedness was controlled by using genomic control. Genetic association was assessed with 2,241,249 single nucleotide polymorphisms (SNPs) in 1300 samples after adjusting for age and gender. Our study replicated four previously reported SUA loci (SLC2A9, ABCG2, RREB1, and SLC22A12). The strongest association was found with a SNP in SLC2A9 (rs13129697, P=2.33×10(-19)), which exhibited significant gender-specific effects, 35.76 µmol/L (P=2.11×10(-19)) in females and 19.58 µmol/L (P=5.40×10(-5)) in males. Within this region of high linkage disequilibrium, we also detected a strong association with a nonsynonymous SNP, rs16890979 (P=2.24×10(-17)), a putative causal variant for SUA variation. In addition, we identified several novel loci suggestive of association with uric acid levels (SEMA5A, TMEM18, SLC28A2, and ODZ2), although the P-values (P<5×10(-6)) did not reach the threshold of genome-wide significance. Together, these findings provide further confirmation of previously reported uric-acid-related genetic variants and highlight suggestive new loci for additional investigation.

Influence of evolutionary forces and demographic processes on the genetic structure of three Croatian populations: a maternal perspective.

BACKGROUND: Many Croatian islands are examples of genetic isolates, with low level of heterozygosity and high level of inbreeding, due to practice of endogamy. AIM: The aim was to study the genetic structure of two insular and one mainland population through high-resolution phylogenetic analysis of mitochondrial DNA (mtDNA). SUBJECTS AND METHODS: MtDNA polymorphisms were explored in 300 unrelated individuals from Mljet, Lastovo and the coastal city of Dubrovnik, based on SNP polymorphisms. RESULTS: All mtDNA haplogroups found in the sample were of typical European origin. However, the frequency distribution of their subclades differed significantly from other Croatian and European populations. MtDNA haplotype analysis revealed only two possible founder lineages on Mljet and six on Lastovo, accounting for almost half of the sample on both islands. The island of Mljet also has the lowest reported haplotype and nucleotide diversity among Croatian isolates and the island of Lastovo, a new sublineage of a usually quite rare U1b clade. CONCLUSION: The results can be explained by the effect evolutionary forces have on genetic structure, which is in line with the specific demographic histories of the islands. An additional research value of these two island isolates is the appearance of certain Mendelian disorders, highlighting their importance in epidemiological studies.