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.

Three Patterns of Inheritance of Quantitative Dermatoglyphic Traits: Kosovo Albanian Twin Study.

Dermatoglyphs are epidermal ridge configurations on the fingers, palms and soles that are formed during fetal development, and therefore only the intrauterine environment can have any influence on their formation. This study aims at investigating the genetic and environmental contribution in determining quantitative dermatoglyphic traits in 32 monozygotic (MZ) and 35 dizygotic (DZ) same-sex twins from the Albanian population of Kosovo. All genetic analyses were run in the statistical program Mx. After assumptions testing, based on the pattern of MZ-DZ correlations, univariate models were fitted to the data in order to estimate additive genetic (A), common (C) and individual (E) environmental influences for all variables. The exception was the atd-angle for which a model with nonadditive genetic (D) influences was tested, since DZ correlations were less than half of MZ correlations. Goodness of fit of the full ACE or ADE model was compared to the saturated model. The fit of nested models (AE, CE, DE or E) was compared to the full models (ACE or ADE). Our results indicate that additive genetic component strongly contributes to individual differences in finger ridge counts (49-81%), and weakly (0-50%) on the formation of the palmar ridge counts between the palmar triradii a, b, c, and d. The specific pattern found for the atd-angle implies the impact of a nonadditive genetic component, possibly the effect of a major gene. Further, more powered studies are needed to confirm this pattern, especially for resolving the issue of the huge difference in MZ and DZ twin similarity for the atd-angle palmar trait.

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.

The role of longevity-related genetic variant interactions as predictors of survival after 85 years of age.

Genome-wide association studies and candidate gene studies have identified several genetic variants that might play a role in achieving longevity. This study investigates interactions between pairs of those single nucleotide polymorphisms (SNPs) and their effect on survival above the age of 85 in a sample of 327 Croatian individuals. Although none of the SNPs individually showed a significant effect on survival in this sample, 14 of the 359 interactions tested (between SNPs not in LD) reached the level of nominal significance (p<0.05), showing a potential effect on late-life survival. Notably, SH2B3 rs3184504 interacted with different SNPs near TERC, TP53 rs1042522 with different SNPs located near the CDKN2B gene, and CDKN2B rs1333049 with different SNPs in FOXO3, as well as with LINC02227 rs2149954. The other interaction pairs with a possible effect on survival were FOXO3 rs2802292 and ERCC2 rs50871, IL6 rs1800795 and GHRHR rs2267723, LINC02227 rs2149954 and PARK7 rs225119, as well as PARK7 rs225119 and PTPN1 rs6067484. These interactions remained significant when tested together with a set of health-related variables that also had a significant effect on survival above 85 years. In conclusion, our results confirm the central role of genetic regulation of insulin signalling and cell cycle control in longevity.

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.

Genes Involved in DNA Damage Cell Pathways and Health of the Oldest-Old (85+).

Some sources report a connection of cellular senescence with chronic pathological conditions; however, the association between particular cellular processes and general health is rarely examined. This study aims to test the relationship of general health with DNA damage pathways that play a crucial role in senescence. The association of ten selected SNPs with subjective and objective general health and functional ability indicators has been tested in 314 oldest-old people from Croatia. Multivariate logistic regression was employed to simultaneously test the impact of variables potentially influencing targeted health and functional ability variables. The best model, explaining 37.1% of the variance, has six independent significant predictors of functional ability scores: rs16847897 in TERC, rs533984 in MRE11A, and rs4977756 in CDKN2B, chronic disease count, Mini-Mental State Examination scores, and age at surveying. In conclusion, the examined ten loci involved in DNA damage repair pathways showed a more significant association with self-rated health and functional ability than with the number of disease or prescribed medicaments. The more frequent, longevity-related homozygote (GG) in rs16847897 was associated with all three aspects of self-assessments-health, mobility, and independence-indicating that this TERC locus might have a true impact on the overall vitality of the oldest-old persons.

Genetic scores for predicting longevity in the Croatian oldest-old population.

Longevity is a hallmark of successful ageing and a complex trait with a significant genetic component. In this study, 43 single nucleotide polymorphisms (SNPs) were chosen from the literature and genotyped in a Croatian oldest-old sample (85+ years, sample size (N) = 314), in order to determine whether any of these SNPs have a significant effect on reaching the age thresholds for longevity (90+ years, N = 212) and extreme longevity (95+ years, N = 84). The best models were selected for both survival ages using multivariate logistic regression. In the model for reaching age 90, nine SNPs explained 20% of variance for survival to that age, while the 95-year model included five SNPs accounting for 9.3% of variance. The two SNPs that showed the most significant association (p ≤ 0.01) with longevity were TERC rs16847897 and GHRHR rs2267723. Unweighted and weighted Genetic Longevity Scores (uGLS and wGLS) were calculated and their predictive power was tested. All four scores showed significant correlation with age at death (p ≤ 0.01). They also passed the ROC curve test with at least 50% predictive ability, but wGLS90 stood out as the most accurate score, with a 69% chance of accurately predicting survival to the age of 90.

From Croatian Roma to 1000 Genomes: The Story of the CYP2D6 Gene Promoter and Enhancer SNPs.

The CYP2D6 gene encodes an enzyme responsible for the metabolism of ~20% of clinically prescribed drugs. In this study, 18 SNPs from the enhancer and promoter regions of CYP2D6 in 323 Roma from Croatia were genotyped, to find out whether the demographic history of Roma affected the distribution of the studied SNPs and their linkage disequilibrium (LD) values, with the major SNPs defining the CYP2D6 star alleles. No differences were found between the three Roma groups in allele and genotype frequencies. The distribution of LD values of Roma was compared with LD values of European and Asian populations. Regulatory CYP2D6 SNPs (rs5758550, rs28624811, rs1080985 and rs1080983) showed similar distribution and the highest LDs with rs16947 from the gene-coding region in all populations. In the promoter region, a complete LD between rs1080989 and rs28588594, and between rs1080983 and rs28624811, was found in Croatian Roma and investigated populations from 1000 genomes. A high LD was also found between rs1080985 from the promoter and rs5758550 from the enhancer region. SNP rs28735595 from the gene promoter region had the highest LD, with two gene region SNPs, rs1058164 and rs1135840. To conclude, the Croatian Roma population shows an LD pattern of the CYP2D6 gene region similar to the 1000 Genomes European and Asian populations.

Untangling SNP Variations within CYP2D6 Gene in Croatian Roma.

CYP2D6 is a highly polymorphic gene whose variations affect its enzyme activity. To assess whether the specific population history of Roma, characterized by constant migrations and endogamy, influenced the distribution of alleles and thus phenotypes, the CYP2D6 gene was sequenced using NGS (Next Generation Sequencing) method-targeted sequencing in three groups of Croatian Roma (N = 323) and results were compared to European and Asian populations. Identified single nucleotide polymorphisms (SNPs) were used to reconstruct haplotypes, which were translated into the star-allele nomenclature and later into phenotypes. A total of 43 polymorphic SNPs were identified. The three Roma groups differed significantly in the frequency of alleles of polymorphisms 6769 A > G, 6089 G > A, and 5264 A > G (p < 0.01), as well as in the prevalence of the five most represented star alleles: *1, *2, *4, *10, and *41 (p < 0.0001). Croatian Roma differ from the European and Asian populations in the accumulation of globally rare SNPs (6089 G > A, 4589 C > T, 4622 G > C, 7490 T > C). Our results also show that demographic history influences SNP variations in the Roma population. The three socio-culturally different Roma groups studied differ significantly in the distribution of star alleles, which confirms the importance of a separate study of different Roma groups.

Relevance of CYP2D6 Gene Variants in Population Genetic Differentiation.

A significant portion of the variability in complex features, such as drug response, is likely caused by human genetic diversity. One of the highly polymorphic pharmacogenes is CYP2D6, encoding an enzyme involved in the metabolism of about 25% of commonly prescribed drugs. In a directed search of the 1000 Genomes Phase III variation data, 86 single nucleotide polymorphisms (SNPs) in the CYP2D6 gene were extracted from the genotypes of 2504 individuals from 26 populations, and then used to reconstruct haplotypes. Analyses were performed using Haploview, Phase, and Arlequin softwares. Haplotype and nucleotide diversity were high in all populations, but highest in populations of African ancestry. Pairwise FST showed significant results for eleven SNPs, six of which were characteristic of African populations, while four SNPs were most common in East Asian populations. A principal component analysis of CYP2D6 haplotypes showed that African populations form one cluster, Asian populations form another cluster with East and South Asian populations separated, while European populations form the third cluster. Linkage disequilibrium showed that all African populations have three or more haplotype blocks within the CYP2D6 gene, while other world populations have one, except for Chinese Dai and Punjabi in Pakistan populations, which have two.

E2 allele of the apolipoprotein E gene polymorphism is predictive for obesity status in Roma minority population of Croatia.

BACKGROUND AND AIMS: The Roma (Gypsies) are a transnational minority, founder population characterized by unique genetic background modeled by culturally determined endogamy. The present study explores whether the widely found cardiovascular diseases (CVD) risk effects of ACE I/D, APOE (ε2, ε3, ε4), eNOS-VNTR and LEP G2548A polymorphisms can be replicated in this specific population. METHODS AND RESULTS: The community-based study was carried on 208 adult Bayash Roma living in rural settlements of eastern and northern Croatia. Risk effect of four CVD candidate polymorphisms are related to the most prominent classical CVD risk phenotypes: obesity indicators (body mass index and waist circumference), hypertension and hyperlipidemia (triglycerides, HDL and LDL cholesterol). For all of them the standard risk cut-offs were applied. The extent to which the phenotypic status is related to genotype was assessed by logistic regression analysis. The strongest associations were found for ε2 allele of the APOE as a predictor of waist circumference (OR 3.301; 95%CI 1.254-8.688; p = 0.016) as well as for BMI (OR 3.547; 95%CI 1.471-8.557; p = 0.005). It is notable that ε3 allele of APOE gene turned out to be a protective genetic factor determining low lipid levels. CONCLUSION: The strength of the relation and the similarity of the results obtained for both tested indicators of obesity provide firm evidence that APOE plays an important role in obesity development in the Roma population.

CVD Risk Factors in the Ukrainian Roma and Meta-Analysis of Their Prevalence in Roma Populations Worldwide.

The Roma population suffers from severe poverty, social exclusion, and some of the worst health conditions in the industrialized world. Herein, we report on cardiovascular disease (CVD) risk factors in the Ukrainian Roma and present a meta-analysis of the prevalence of CVD risk factors in 16 Roma populations worldwide. The meta-analyses of CVD risk factors in Roma (n = 16,552) vs. non-Roma majority population of the same country (n = 127,874) included publicly available data. Ukrainian field survey included 339 adults of both sexes and outcomes of interest were hypertension, body mass index (BMI), smoking, education, and employment status. Furthermore, 35.7% of the Ukrainian Roma were hypertensive, 69.3% unemployed, and 48.4% never went to school. Ukrainian Roma women were more likely to be underweight and more prone to be hypertensive, with odds of hypertension increasing with age, BMI, and positive smoking status. Meta-analyses showed that, in comparison with non-Roma worldwide, the Roma bear significantly higher risk factor loads related to smoking (OR = 2.850), diabetes (OR = 1.433), abdominal obesity (OR = 1.276), and metabolic syndrome (OR = 1.975), with lower loads for hypertension (OR = 0.607) and BMI ≥ 25 kg/m2 (OR = 0.872). To conclude, the CVD risk factors which are more common in Roma than in the majority population may reflect their poor health-related behaviors and inadequate access to health education.

Global variability of the human IgG glycome.

Immunoglobulin G (IgG) is the most abundant serum antibody which structural characteristics and effector functions are modulated through the attachment of various sugar moieties called glycans. Composition of the IgG N-glycome changes with age of an individual and in different diseases. Variability of IgG glycosylation within a population is well studied and is known to be affected by both genetic and environmental factors. However, global inter-population differences in IgG glycosylation have never been properly addressed. Here we present population-specific N-glycosylation patterns of IgG, analyzed in 5 different populations totaling 10,482 IgG glycomes, and of IgG's fragment crystallizable region (Fc), analyzed in 2,579 samples from 27 populations sampled across the world. Country of residence associated with many N-glycan features and the strongest association was with monogalactosylation where it explained 38% of variability. IgG monogalactosylation strongly correlated with the development level of a country, defined by United Nations health and socioeconomic development indicators, and with the expected lifespan. Subjects from developing countries had low levels of IgG galactosylation, characteristic for inflammation and ageing. Our results suggest that citizens of developing countries may be exposed to environmental factors that can cause low-grade chronic inflammation and the apparent increase in biological age.

Comparative analysis of dermatoglyphic traits in Albanian and Turkish population living in Kosovo.

The aim of the study was to compare quantitative dermatoglyphic traits of two ethnic groups with different origin and customs, living on the same territory. The dermatoglyphic prints were collected from 800 inhabitants of the Dukagjin valley in southwest Kosovo, of Albanian (400) and Turkish (400) ethnic origin. The quantitative analysis comprised the number of ridges and triradii on the fingers, and the number of ridges in the interdigital areas on the palm (a-b, b-c, and c-d) as well as the size of the atd angle. The statistical analysis showed significant differences between the Albanian and the Turkish males for two fingers and pattern intensity index left, and on palms for a-b rc and c-d rc on both hands and b-c re on the left hand, and between females for six fingers and almost all palmar traits. Significant inter-population variations were observed for most palmar areas in both sexes but more pronouncedly in females. The differences found between the examined population groups show that admixture between Albanian and Turkish population in Kosovo has been small, and the Turks have retained their ethnic identity for several centuries.

Waist to height ratio is the anthropometric index that most appropriately mirrors the lifestyle and psychological risk factors of obesity.

AIM: To determine to what extent the lifestyle and psychological factors influenced the occurrence of obesity in the population of the Mediterranean island of Vis (Croatia); also to relate the examined risk factors to several obesity indicators in order to select the most sensitive one. METHODS: Cross-sectional population study included 960 participants of both sexes (18-93 years) in whom the obesity was estimated using anthropometric indicators. The factor analysis of 55-item Food Frequency Questionnaire (FFQ) was performed as well as the General Health Questionnaire (GHQ12) for the self-assessment of psychological health and wellbeing. FFQ and GHQ12 individual factors' scores, sex, age, physical activity, smoking and socioeconomic status were further used as independent variables in the multiple linear regression analyses with five obesity indicators as dependent variables. RESULTS: The examined risk factors explained the highest proportion of variance of the waist to height ratio (WHtR) in comparison with all other indicators of obesity (body mass index (BMI), waist to hip ratio, sum of skinfolds thicknesses, fat mass percentage). Only the dietary factors showed a significant relation to BMI, while almost all of the tested variables-dietary pattern, psychological structure, smoking habit and physical activity-had a significant association with WHtR. CONCLUSIONS: WHtR is the most useful indicator of obesity as it had a profiled relation with a number of lifestyle factors as well as with psychological health. The present study also revealed the importance of psychological factors for obesity phenotype, particularly the behavioural pattern which could be described as avoidance of dealing with problems.

The prevalence of lateral incisor hypodontia and canine impaction in Croatian population.

The study investigates the prevalence of second incisor hypodontia and canine impaction in Croatia. The study of incisor hypodontia encompassed 568 examinees (229 boys, 339 girls) aged 6-22 (X = 11.2, SD = 2.8) while for canine impaction, a subsample of 170 examinees older than 13 years was formed (68 boys and 102 girls). The participants were non-selected ambulatory patients of the Dental Clinic Zagreb and the School of Dental Medicine, University of Zagreb who voluntarily participated in the study. Investigated anomalies were registered from panoramic x-rays and dental records and a tooth was diagnosed as congenitally missing when no crown mineralization could be identified on dental panoramic tomogram and no evidence of extraction was found. For each examinee, the final dental panoramic tomogram evaluation was performed at the age of 13 years. Missing lateral incisors are found in 14 out of 568 participants, indicating the prevalence of 2.46%. With the M : F ratio 1 : 6, sex-specific prevalence are 0.87% and 3.54% for males and females respectively. The prevalence of missing lateral incisor is 1.76% in maxilla and 0.70% in mandible. The sex specific pattern as well as overall prevalence of lateral incisor hypodontia is within the range reported in other studies. On the other hand, the findings of bilaterally missing lateral incisor in six out of 14 examinees (or in 42.86% of hypodontia) is certainly the specificity of the here investigated population. The additional peculiarity is the finding of the bilateral aplasia of mandible canines registered in one child. Canine impaction is found in 8 participants of the present study (4.71%) and in all cases it was placed in maxilla. No sex specific differences in prevalence of impactions are found. In one case (or in 12.5%) a canine impaction is found bilaterally. Missing lateral incisors and canine impaction in the same examinee was not found in this study.

Gender-specific growth patterns of transversal body dimensions in Croatian children and youth (2 to 18 years of age).

In a cross-sectional study of growth, 5,260 healthy children of both sexes from Zagreb (Croatia) aged 2 to 18 years were measured. Six transversal body dimensions were studied: biacromial, transverse chest, antero-posterior chest, biiliocristal, bicondylar humerus and bicondylar femur diamters. A significant increase in body diameters has been observed until the age of 14 to 15 in girls and until the age of 16 in boys, showing that girls have a 1 to 2 years shorter period of growth. Compared to boys of the same age, they achieved larger amounts of final transversal bone size throughout the whole growth period. The most pronounced example was the knee diameter that in girls attained 95% of adult size as early as the age of 10. In both genders, the adult size is achieved earlier in widths of the extremities than in those of the trunk. The studied transversal body segments showed different growth dynamics, which is gender-specific. While sexual dimorphism in pelvic and shoulder diameters emerged with pubertal spurt, gender differences in chest and extremities' diameters started early in life. In all ages, boys had larger chest, elbow and knee diameters. In pubertal age boys gained a significantly larger biacromial diameter (from the age of 13 onwards), while girls exceeded them in biiliocristal diameter (from 10 to 14 years). The findings of gender differences were compared to those reported for other European populations and their growth patters were discussed comparing viewpoints.

Traditional CVD risk factors and socio-economic deprivation in Roma minority population of Croatia.

Researches into health inequalities consistently show disadvantages in health status, morbidity and mortality for various ethnic minority groups. Current knowledge about prevention of cardiovascular diseases (CVD) mainly derives from studies carried out in populations of European origin while the evidences involving Roma population are scarce. Roma, an ethnic minority of northern Indian origin, live in many countries throughout the world and are well known for preserved traditions and resistance to assimilation. They are most often marginalized economically, spatially, politically and in terms of culture. In order to assess the health status and health-related lifestyle attributes, a multidisciplinary anthropological and epidemiological community-based study was carried out including a total of 423 members of the Bayash Roma minority population living in two regions of Croatia (144 men and 279 women, aged 18-84 yrs). Hypertension (HT) was found in 24.8% Bayash Roma (21.5% men and 26.5% women) using standard diagnostic criteria (i.e. BP > or = 140/90 mm Hg or taking antihypertensive therapy). The prevalence increases from 5.9% in the age group 18-34 yrs; 35.0% in the age group 35-64 yrs, and 51.4% in the age group 65+ yrs. The prevalence of hypertension in the Bayash Roma is almost half of the magnitude of what is usually reported for the general population of Croatia. It is also lower when compared with other European populations and this finding is not due to comparatively younger average age of the Bayash sample. The significant association of hypertension with age and BMI was confirmed in this study and the importance of non-traditional SES-related CVD risk factors was highlighted. Smoking is a part of traditional Roma life-style and with 70% of smokers almost the entire population is equally exposed to this risk factor in their family environment. Since homogenously distributed, this risk factor did not show to be a significant predictor of hypertension. The extent to which hypertension is influenced by traditional CVD risk factors as well as by some SES indicators was also assessed using a forward stepwise method of the multivariate logistic analysis. Each risk factor was explored as quantitative variable as well as qualitative one using various cut-offs. The best model showed to be the one having age and BMI presented as quantitative variables and sex, region, smoking status, income and schooling years as categorical ones; with cut-off 3 for number of income sources and 8 for the number of schooling years. In spite of the low prevalence of hypertension, the presented results are showing that Bayash Roma are bearing a high CVD risk factors load. We expect that with westernization of their life-style and along with increase of the economic power, the proportion of CVD in population of Bayash Roma will also increase. Therefore, it is important to recognize the need for early cardiovascular disease risk factors prevention in this minority population.

Characterization of ADME genes variation in Roma and 20 populations worldwide.

The products of the polymorphic ADME genes are involved in Absorption, Distribution, Metabolism, and Excretion of drugs. The pharmacogenetic data have been studied extensively due to their clinical importance in the appropriate drug prescription, but such data from the isolated populations are rather scarce. We analyzed the distribution of 95 polymorphisms in 31 core ADME genes in 20 populations worldwide and in newly genotyped samples from the Roma (Gypsy) population living in Croatia. Global distribution of ADME core gene loci differentiated three major clusters; (1) African, (2) East Asian, and (3) joint European, South Asian and South American cluster. The SLCO1B3 (rs4149117) and CYP3A4 (rs2242480) genes differentiated at the highest level the African group of populations, while NAT2 gene loci (rs1208, rs1801280, and rs1799929) and VKORC1 (rs9923231) differentiated East Asian populations. The VKORC1 rs9923231 was among the investigated loci the one with the largest global minor allele frequency (MAF) range; its MAF ranged from 0.027 in Nigeria to 0.924 in Han Chinese. The distribution of the investigated gene loci positions Roma population within the joined European and South Asian clusters, suggesting that their ADME gene pool is a combination of ancestral (Indian) and more recent (European) surrounding, as it was already implied by other genetic markers. However, when compared to the populations worldwide, the Croatian Roma have extreme MAF values in 10 out of the 95 investigated ADME core gene loci. Among loci which have extraordinary MAFs in Roma population two have strong proof of clinical importance: rs1799853 (CYP2C9) for warfarin dosage, and rs12248560 (CYP2C19) for clopidogrel dosage, efficacy and toxicity. This finding confirms the importance of taking the Roma as well as the other isolated populations`genetic profiles into account in pharmaco-therapeutic practice.

Trapped between tradition and transition--anthropological and epidemiological cross-sectional study of Bayash Roma in Croatia.

AIM: To assess the key characteristics related to living conditions and health in the Bayash Roma population in Baranja and Medimurje regions of Croatia and identify possible demographic and socio-economic sources of variance in self-reported health and reproductive profile. METHODS: The study comprised a total of 266 adult Bayash individuals from Baranja and 164 from Medimurje (aged 41.3+/-15.1 years). Data on ethno-historical and demographic background, self-identity, life and hygiene conditions, education, employment, health insurance, and health (dietary and smoking habits, reproductive characteristics, diagnosed and undiagnosed health problems, use of medications). were obtained through interviews. Bivariate and multivariate methods were used in statistical analyses. RESULTS: The reported migratory pattern demonstrated that 88.8% of the examinees were born in the region of residence, which showed that the Bayash population was autochthonous and sedentary one. Financially, the Bayash primarily relayed on social welfare support allowance (84%) and child allowance (47%), while merely 2% were permanently and 23% occasionally employed. The proportion of the Bayash who had never attended school amounted to 33.3% (19.3% men and 40.6% women). The access to public water supply system was available to 52.5% of examinees, whereas only 1.7% had public sewage system, and 23.4% had private septic tanks. The most commonly reported health burden were frequent headaches (20.3%), stomach pain (16.3%), anxiety or insomnia (13.1%), hypertension (9.3%), and chronic obstructive pulmonary disease (COPD) (8.6%). The logistic regression identified level of education (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.63-0.94) and access to health insurance (OR, 4.32; 95% CI, 1.46-12.77) as socio-economic/life-style factors playing a significant role in the occurrence of COPD. CONCLUSION: Our results indicate poor inclusion of the Bayash in the essential social service sectors such as health care, education, and employment, as well as substandard living conditions and unfavorable health-related behavior. Since education and health insurance were found to have significant effects on the observed reproductive status and self-reported health, they should be targeted in planning public health actions for socially marginalized and economically deprived groups.