Calcaneous Ultrasonographic Assessment of Bone Mineral Density in the Roma Minority Population of Croatia – Preliminary Report

A multidisciplinary anthropological and epidemiological pilot field study of the Bayash population living in 6 villages of the eastern Croatian region of Baranya has been performed in 2005/06. The Bayash (or Boyash) belong to the Roma minority population speaking a distinct archaic dialect of the Romanian language. Since the bone mineral density values in the Roma have not been explored so far and the prevalence of osteoporosis is unknown for this ethnic minority group a screening by means of the »Sahara« Hologic clinical bone sonometer has been performed on 232 voluntary participants (73 males and 159 females). The prevalence of osteoporosis (T-score <–2.5) in the Bayash aged 50 and older is found to be 9.1% in males and 34.4% in females, which is substantially higher than in the general population of Croatia. The prevalence of T-values ranging from –1 to –2.5 indicating osteopenia is found to be 63.6% in males and 45.3% in females, while T-values within the normal range are found only in 27.3% males and 20.3% females. In addition to the low bone mass in older subjects, the mean estimated bone mineral density in all age groups of Bayash men and women was lower in comparison to the manufacturer’s reference ranges for European population of the same age. Since body size effects could not be declined, the reference values that would be appropriate for the Roma population should be further explored. The high estimated prevalence of developed osteoporosis calls for attention and the survey should also be extended to exploring the association of low bone mineral density with particular life style and reproductive factors present in this semi-sedentary Roma population

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

<p>Abstract</p> <p>Background and Aims</p> <p>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.</p> <p>Methods and Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

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

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 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 comparative 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

The role of the Vlax Roma in shaping the European Romani maternal genetic history

The Roma are comprised of many founder groups of common Indian origins but different socio-cultural characteristics. The Vlax Roma are one of the founder Roma populations characterized by a period of bondage in the historic Romanian principalities, and by the archaic Romanian language. Demographic history suggests different migration routes of Roma populations, especially after their arrival in Mesopotamia and the eastern boundary of the Byzantine Empire. Although various genetic studies of uniparental genetic markers showed a connection between Roma genetic legacy and their migration routes, precise sampling of Roma populations elucidates this relationship in more detail. In this study, we analyzed mitochondrial DNA of 384 Croatian Vlax Roma from two geographic locations in the context of 734 European Roma samples. Our results show that Roma migration routes are marked with two Near-Eastern haplogroups, X2 and U3, whose inverse proportional incidence clearly separates the Balkan and the Vlax Roma from other Roma populations that reached Europe as part of the first migration wave. Spatial and temporal characteristics of these haplogroups indicate a possibility of their admixture with Roma populations before arrival in Europe. Distribution of haplogroup M35 indicates that all Vlax Roma populations descend from one single founder population that might even reach back to the original ancestral Indian population. Founder effects followed by strict endogamy rules can be traced from India to contemporary small, local communities, as in the case of two Croatian Vlax Roma populations that show clear population differentiation despite similar origins and shared demographic history

Calcaneous Ultrasonographic Assessment of Bone Mineral Density in the Roma Minority Population of Croatia – Preliminary Report

A multidisciplinary anthropological and epidemiological pilot field study of the Bayash population living in 6 villages of the eastern Croatian region of Baranya has been performed in 2005/06. The Bayash (or Boyash) belong to the Roma minority population speaking a distinct archaic dialect of the Romanian language. Since the bone mineral density values in the Roma have not been explored so far and the prevalence of osteoporosis is unknown for this ethnic minority group a screening by means of the »Sahara« Hologic clinical bone sonometer has been performed on 232 voluntary participants (73 males and 159 females). The prevalence of osteoporosis (T-score <–2.5) in the Bayash aged 50 and older is found to be 9.1% in males and 34.4% in females, which is substantially higher than in the general population of Croatia. The prevalence of T-values ranging from –1 to –2.5 indicating osteopenia is found to be 63.6% in males and 45.3% in females, while T-values within the normal range are found only in 27.3% males and 20.3% females. In addition to the low bone mass in older subjects, the mean estimated bone mineral density in all age groups of Bayash men and women was lower in comparison to the manufacturer’s reference ranges for European population of the same age. Since body size effects could not be declined, the reference values that would be appropriate for the Roma population should be further explored. The high estimated prevalence of developed osteoporosis calls for attention and the survey should also be extended to exploring the association of low bone mineral density with particular life style and reproductive factors present in this semi-sedentary Roma population

Dissecting the molecular architecture and origin of Bayash Romani patrilineages: genetic influences from South-Asia and the Balkans

The Bayash are a branch of Romanian speaking Roma living dispersedly in Central, Eastern, and Southeastern Europe. To better understand the molecular architecture and origin of the Croatian Bayash paternal gene pool, 151 Bayash Y chromosomes were analyzed for 16 SNPs and 17 STRs and compared with European Romani and non-Romani majority populations from Europe, Turkey, and South Asia. Two main layers of Bayash paternal gene pool were identified: ancestral (Indian) and recent (European). The reduced diversity and expansion signals of H1a patrilineages imply descent from closely related paternal ancestors who could have settled in the Indian subcontinent, possibly as early as between the eighth and tenth centuries AD. The recent layer of the Bayash paternal pool is dominated by a specific subset of E1b1b1a lineages that are not found in the Balkan majority populations. At least two private mutational events occurred in the Bayash during their migrations from the southern Balkans toward Romania. Additional admixture, evident in the low frequencies of typical European haplogroups, J2, R1a, I1, R1b1b2, G, and I2a, took place primarily during the early Bayash settlement in the Balkans and the Romani bondage in Romania. Our results indicate two phenomena in the Bayash and analyzed Roma: a significant preservation of ancestral H1a haplotypes as a result of considerable, but variable level of endogamy and isolation and differential distribution of less frequent, but typical European lineages due to different patterns of the early demographic history in Europe marked by differential admixture and genetic drift

Y-STR genetic diversity of Croatian (Bayash) Roma

Seventeen Y-chromosomal short tandem repeats (STRs) (DYS19, DYS385, DYS389I, DYS398II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATA H4.1) were typed in DNA samples from 146 unrelated adult Romani Bayash men from eastern and northwestern Croatia. Analysed Croatian Bayash Romani population represents an example of genetically homogenous population characterised by low levels of haplotype diversity and unique haplotype ratio as well as sharing of the same most frequent (founding) haplotype and its close derivatives by more than one third of the analyzed men. Despite almost exclusive sharing of the same minimal haplotype and its closely related derivates on the background of the Indian Y SNP haplogroup H1, we observed considerable level of genetic differentiation of Romani populations across Europe that should not be neglected in forensic statistics

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

Relevance of <i>CYP2D6</i> 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