Different expression of DNMT1, PCNA, MCM2, CDT1, EZH2, GMNN and EP300 genes in lymphomagenesis of low vs. high grade lymphoma.

Tumour cells develop by accumulating changes in the genome that result in changes of main cellular processes. Aberrations of basic processes such as replication and chromatin reassembly are particularly important for genomic (in)stability. The aim of this study was to analyse the expression of genes whose products are crucial for the regulation of replication and chromatin reassembly during lymphomagenesis (DNMT1, PCNA, MCM2, CDT1, EZH2, GMNN, EP300). Non-tumour B cells were used as a control, and follicular lymphoma (FL) and the two most common groups of diffuse large B cell lymphoma (DLBCL) samples were used as a model for tumour progression. The results showed that there are significant changes in the expression of the analysed genes in lymphomagenesis, but also that these changes do not display linearity when assessed in relation to the degree of tumour aggression. Additionally, an integrated bioinformatics analysis of the difference in the expression of selected genes between tumour and non-tumour samples, and between tumour samples (FL vs. DLBCL) in five GEO datasets, did not show a consistent pattern of difference among the datasets.

Association of perfluoroalkyl substances exposure with cardiometabolic traits in an island population of the eastern Adriatic coast of Croatia.

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.

Distinctiveness of the Roma population within CYP2B6 worldwide variation.

AIM: To determine variation of CYP2B6 gene within the genetically specific Croatian Roma (Gypsy) population originating from India and to examine it in the worldwide perspective. MATERIALS & METHODS: Seven SNP loci (rs12721655, rs2279343, rs28399499, rs34097093, rs3745274, rs7260329 and rs8192709) were genotyped in 439 subjects using Kompetitive Allele Specific PCR (KASP) method. RESULTS: The Croatian Roma took an outlying position in CYP2B6 variation from the worldwide perspective mainly due to their exceptionally high minor allele frequency (MAF) for rs8192709 (12.8%), and lower for rs2279343 (21.1%) compared with south Asian populations. CONCLUSION: This study provides the first data of several CYP2B6 polymorphisms in Roma population and indicates the need for systematic investigation of the most important pharmacogenes' variants in this large, transnationally isolated population worldwide.

Novel locus for fibrinogen in 3' region of LEPR gene in island population of Vis (Croatia).

Leptin, a possible mediator between energy homeostasis, inflammation and cardiovascular disease (CVD), acts via leptin receptors. We investigated association of single-nucleotide polymorphisms (SNPs) and haplotypes of the leptin receptor gene (LEPR) with several CVD risk factors: body mass index, waist circumference (WC), serum lipids, fibrinogen and C-reactive protein levels. Thirty-one SNPs in and near LEPR gene were analyzed in 986 inhabitants of the island of Vis, Croatia and 29 SNPs in the inland sample (N=499). We assessed linkage disequilibrium (LD), SNP and haplotype associations with the selected phenotypes. rs4291477 significantly associated with fibrinogen (P=0.003) and rs7539471 marginally significantly with high-density lipoprotein (P=0.004), but only in the Vis sample, while rs10493384 marginally significantly associated with triglyceride levels (P=0.006) in the inland sample. SNPs were grouped into eight LD blocks in Vis and in seven blocks in the inland population. Haplotype A-C-A-A-G-A in block 5 in Vis (rs1782754, rs1171269, rs1022981, rs6673324, rs3790426, rs10493380) and haplotype A-A-A-A in block 4 in the inland data (rs1782754, rs1022981, rs6673324, rs1137100) were nominally associated with WC, P=7.085 × 10(-22) (adjusted P=0.0979) and P=5.496 × 10(-144) (adjusted P=0.1062), respectively.

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-valutes (Pgirls<0.05, Pboys<0.001); additionally, boys had higher Z-values for body weight (p<0.05) and triceps/subscaputar 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.

Age trends in prevalence of cardiovascular risk factors in Roma minority population of Croatia.

The Roma (Gypsy) are the largest European minority population characterized by poverty, social exclusion as well as by numerous life-style and cultural specificities, which all could have an adverse impact on their cardiovascular health. This study assesses the prevalence of cardiovascular diseases (CVD) risk factors in community-based sample of 430 adult Roma, living in rural area of Croatia, by providing the actual and age-adjusted estimates using the European standard population. The most prominent classical CVD risk phenotypes (blood pressure, obesity, smoking, glucose and lipid profile) were selected, and the standard risk cut-offs were applied. The study has shown that compared to general population of Croatia, the Roma population bears a high CVD risk factors load related to smoking and high glucose level. The CVD risk factors prevalence in Roma also showed important sex and age patterns, the most imposing of which are the findings of higher prevalence of CVD risks in women (especially obesity and triglyceride levels) and the trend of higher body mass index (BMI) level in younger age group (18-34 years) which both stand in contrast to the trends characterizing the general population of Croatia. These findings are complemented by the trend of decreased risk in the oldest age group (65+ years) for all investigated CVD risk factors (with exception of triglycerides level) compared to the 50-64 age group. We conclude that the age and sex CVD risks pattern point to the health transition of this rural Roma population. As we expect the proportion of CVD in the Roma minority of Croatia to increase in the future along with further modernization of their lifestyle, the CVD prevention measures in this population are urgent and should be primarily targeted at women and at the younger segment of this population.

A detection of microevolutionary changes by the analysis of qualitative dermatoglyphic traits: an example of Albanians from Kosovo.

In this study we analyzed the qualitative dermatoglyphic traits in the Albanians from three Kosovo distinct regions. We aimed to detect possible microevolutionary changes, which could have happened as a consequence of geographical and cultural isolation. The dermatoglyphic traits were analyzed for total 641 Albanians of both sexes. The analysis included 4 variables on fingers, 8 on palms and terminations of A, B, C, D and T main-lines. The differences in patterns incidence were tested using the chi-square test. The frequencies of several pattern types varied to a great extent between distinct groups with statistically significant difference in most of the cases. Our results indicated that the Albanians from South Morava valley and from Kosovo plain were genetically close, and the population from Dukagjini valley is less close to any of them. The analysis of qualitative dermatoglyphic patterns may be utilized effectively to track the microevolutionary changes. This is especially useful in a developing country like Kosovo, since it is an inexpensive and effective tool for screening and studying the patterns influenced by the divergence of population.