Search

Cardiovascular disease is the leading cause of death worldwide. Previous studies have found that genetics incompletely explain susceptibility to cardiovascular disease. To find new potential risk factors, the authors investigated the possible contribution of DNA methylation (modifications to DNA that can affect gene expression but do not alter the underlying genetic code) in an adult population on the Croatian island of Hvar, which has a high number of people with cardiovascular and metabolic disease. By examining DNA methylation in blood collected at two time points, 10 years apart, the authors were able to identify DNA methylation that either stayed the same over time (stable) or changed the most over time (dynamic). These were then compared with clinical test results related to cardiovascular or metabolic diseases to determine if they are associated. Twenty-two methylation sites were found to be associated with systolic blood pressure. Of those, 20 were considered stable and two were dynamic. Additionally, there was one stable methylation site associated with serum calcium and one with C-reactive protein. These findings suggest that systolic blood pressure may be regulated through stable DNA methylation that is potentially established earlier in life.

The paper presents an overview of the 50-year long bioanthropological research of the Hvar islanders and depicts the maternal and paternal genetic landscape of the Hvar population (mtDNA and NRY lineages) in more detail. MtDNA haplogroups were determined in 169 and NRY haplogroups in 407 autochthonous individuals from the Hvar Island. The relatively high level of diversity of mtDNA and NRY lineages has been observed, however with interesting deviations from both the maternal (F1b1 lineage) and paternal (Q2a1a lineage) perspective. Additionally, population substructuring revealed differences between Hvar communities (east-west substructuring), in line with the ethnohistoric background and observed migration patterns on the island. Genetic analysis of the Hvar islanders presents a highlight of the 50-year long anthropological research on this island and offers insight into the current genetic structure of Dalmatia, Croatia, shaped by dynamic and diverse population movements throughout history.

Background Exposure to perfluoroalkyl substances (PFAS), ubiquitous environmental contaminants, may be related to cardiometabolic diseases in adults. Studies in European populations to examine the association of PFAS exposure and comprehensive cardiometabolic traits and metabolic syndrome (MetS) are limited. Methods In this pilot cross-sectional study of a well-characterized adult population of the island of Hvar, situated off the eastern Adriatic coast of Croatia, we measured PFAS concentrations in plasma samples collected during 2007–2008 and examined their cross-sectional associations with cardiometabolic traits and MetS after adjustment of covariates (n = 122). PFAS investigated in this study included perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA). Results The geometric mean (range) was 8.91 (2.36, 33.67) ng/mL for PFOS, 2.87 (1.03, 8.02) ng/mL for PFOA, 0.77 (0.25, 2.40) ng/mL for PFHxS, and 1.29 (0.48, 3.46) ng/mL for PFNA, with frequency of detection at 100%, 100%, 95.9%, and 100%, respectively. PFOS, PFOA, and PFNA concentrations were positively associated with the risk of MetS as defined by the Adult Treatment Panel III (ATP III) criteria, with estimated odds ratios and 95% confidence intervals at 1.89 (0.93, 3.86), 2.19 (0.88, 5.44), and 2.95 (1.12, 7.80), respectively, with only PFNA reaching statistical significance. PFNA concentrations were associated with increased risk of overweight or obesity. Conclusions Background exposure to PFOS, PFOA, and PFNA was marginally associated with increased risk of MetS in this small study, and these results should be confirmed with a larger sample size and longitudinal follow-up.

Maternal nutrition and lifestyle in pregnancy are important modifiable factors for both maternal and offspring&rsquo, s health. Although the Mediterranean diet has beneficial effects on health, recent studies have shown low adherence in Europe. This study aimed to assess the Mediterranean diet adherence in 266 pregnant women from Dalmatia, Croatia and to investigate their lifestyle habits and regional differences. Adherence to the Mediterranean diet was assessed through two Mediterranean diet scores. Differences in maternal characteristics (diet, education, income, parity, smoking, pre-pregnancy body mass index (BMI), physical activity, contraception) with regards to location and dietary habits were analyzed using the non-parametric Mann&ndash, Whitney U test. The machine learning approach was used to reveal other potential non-linear relationships. The results showed that adherence to the Mediterranean diet was low to moderate among the pregnant women in this study, with no significant mainland&ndash, island differences. The highest adherence was observed among wealthier women with generally healthier lifestyle choices. The most significant mainland&ndash, island differences were observed for lifestyle and socioeconomic factors (income, education, physical activity). The machine learning approach confirmed the findings of the conventional statistical method. We can conclude that adverse socioeconomic and lifestyle conditions were more pronounced in the island population, which, together with the observed non-Mediterranean dietary pattern, calls for more effective intervention strategies.

Elevated blood pressure (BP) in pregnancy, especially gestational hypertension and preeclampsia, can lead to serious pregnancy complications and adverse birth outcomes. A large body of literature already reported the effect of baseline body mass index (BMI) on changes in blood pressure during pregnancy. The aim of this study was therefore to define trajectory of systolic (SBP) and diastolic (DBP) blood pressure in 308 pregnant participants from the CRIBS study (146 from the mainland and 162 from the islands of Brač and Hvar) and to analyze the association of blood pressure with maternal BMI prior to pregnancy and maternal anthropometry during pregnancy. Pregnant women included in the CRIBS study had no history of chronic diseases. The BP of CRIBS participants was measured at least once in each trimester, and maternal pre-pregnancy weight was self-reported. All analyses were performed using SPSS 10.0. Results showed that pre-pregnancy BMI was the strongest predictor of pregnancy blood pressure. This association was evident for pre-pregnancy BMI independently (p

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

This paper presents a review of the 50-year long anthropological and epidemiological research of the Susak population. Island of Susak is an example of extreme genetic isolate, with a very low level of heterozygosity and a significantly high level of inbreeding, due to the practice of endogamy. Its specific features have put the island in the focus of diverse research during the last five decades and in this study we additionally present new insights into the island’s maternal genetic heritage. For this purpose, mitochondrial DNA (mtDNA) haplogroup diversity was defined based on SNPs of the control and coding region on the sample of 64 autochthonous individuals from the island. Only three main haplogroups were detected – H, T and one W sample, with a limited number of haplotypes, and certain typical European haplogroups (U, K, J, V, X,) were completely absent. Haplotype analysis revealed five possible founder lineages of altogether 16 different haplotypes. Island of Susak also has the second lowest reported GDV (gene diversity index) among Croatian isolates, which is in line with its reduced mtDNA diversity. Since such island communities are most likely to disappear in the near future, we see these results as a valuable contribution for further population genetics and epidemiological studies.

Aging is a complex process of accumulation of molecular, cellular, and organ damage, leading to loss of function and increased vulnerability to disease and finally to death (1). It is well known that lifestyle choices such as smoking and physical activity can hasten or delay the aging process (2). Such observations have led to the search for molecular markers of age that can be used to predict, monitor, and provide insight into age-associated physiological decline and disease. Protein structure is defined by the sequence of nucleotides in the corresponding genes, thus the polypeptide sequence of a protein cannot change with age. However, an important structural and functional element of the majority of proteins are the glycans that participate in virtually all physiological processes (3). Glycans are product of a complex pathway that involves hundreds of different proteins and are encoded in a complex dynamic network of hundreds of genes (4). Epigenetic regulation of gene expression is expected to affect protein glycosylation and several publications recently reported this effect (5–8). Changes in glycosylation with age have been shown over 20 years ago (9) and have also replicated in recent large population studies (10–13). Immunoglobulin G (IgG) is an excellent model glycoprotein because its glycosylation has been well defined (Figure 1), and many important functional effects of alternative IgG glycosylation have been described (14). For example, glycosylation acts as a switch between pro- and anti-inflammatory IgG functionality. Most of the IgG molecules are not sialylated and are proinflammatory. Terminal α2,6-sialylation of IgG glycans decreases the ability of IgG to bind to activating FcγRs and promotes recognition by DC-SIGN, which increases expression of inhibitory FcγRIIB and is anti-inflammatory (15). Another fascinating example is the role of core fucose in the modulation of antibody-dependent cellular cytotoxicity: IgG-containing glycans that lack core fucose have 100-fold increased affinity for FcγRIIIA and are therefore much more efficient in activating antibody-dependent cellular cytotoxicity than fucosylated glycoforms of the same molecule (16). On average, 95% of the IgG population is core fucosylated (12); thus, most of the immunoglobulins have a “safety switch,” which prevents them from activating antibody-dependent cellular cytotoxicity. Malfunction of this system appears to be associated with autoimmune diseases as indicated by both pleiotropic effects of genes that associate with IgG glycosylation on different inflammatory and autoimmune diseases, and the observed alterations in IgG glycosylation in systemic lupus erythematous (17) and many inflammatory diseases (18). Figure 1. UPLC analysis of immunoglobulin G (IgG) glycosylation. Each IgG contains one conserved N-glycosylation site on Asn197 of its heavy chain. Different glycans can be attached to this site and the process seems to be highly regulated. UPLC analysis can reveal ... Interindividual variability of IgG glycosylation in a population is large (12) and it appears to be affected by both variation in DNA sequence (19) and environmental factors (11). Most of the studies that investigated glycosylation changes with age were either of limited size or were performed on the total plasma glycome; thus, in addition to changes in glycosylation, the observed differences reflected changes in the concentration of individual plasma proteins. In this study, we focused on glycosylation of IgG and analyzed more than 5,000 individuals from four different European populations to provide definitive data about changes in IgG glycosylation through the lifetime.

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).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.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.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.

Metabolic syndrome (MetS) is the leading cause of high morbidity and mortality wordlwide, with enormous impact on population health and medical costs. Its prevalence is more than 30% in the general Croatian population, raising up to 50% in certain Croatian island populations. Institute for Anthropological Research is involved in several ongoing projects related to the investigation of MetS and other complex diseases and this presentation offers an overview of its past, present and future activities in this specific field of research.

Many Croatian islands are examples of genetic isolates, with low level of heterozygosity and high level of inbreeding, due to practice of endogamy.The aim was to study the genetic structure of two insular and one mainland population through high-resolution phylogenetic analysis of mitochondrial DNA (mtDNA).MtDNA polymorphisms were explored in 300 unrelated individuals from Mljet, Lastovo and the coastal city of Dubrovnik, based on SNP polymorphisms.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.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.

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.