Ana Barešić

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

Background and AimsThe 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 ResultsThe 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.ConclusionThe 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.

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.

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.

Carrier rates of four single-gene disorders in Croatian Bayash Roma.

To assess how specific population history, different migration routes, isolation, and endogamy practices contributed to the distribution of several rare diseases found in specific Roma groups, we conducted a population-based research study of rare disease mutations in Croatian Vlax Roma. We tested a total of 427 subjects from Baranja and Međimurje for the presence of four mutations causing hereditary motor and sensory neuropathy type Lom (HMSNL), GM1 gangliosidosis (GM1), congenital cataracts, facial dysmorphism and neuropathy (CCFDN), and limb girdle muscle dystrophy type 2C (LGMD2C), using the RFLP-PCR method to estimate carrier frequencies. We identified a total of four individuals heterozygous for the mutation causing HMSNL in the Baranja population, with a carrier rate amounting to 1.5%. Carriers for other three mutations causing GM1, CCFDN, and LGMD2C were not found in our sample. The carrier rate for the HMSNL mutation in Baranja is lower than in other Vlax Roma groups. In addition, distinct differences in carrier rates between the Croatian Vlax groups point to different genetic history, despite their belonging to the same Roma migration category and subgroup. The difference in carrier rates is either the result of admixture or the reflection of a greater extent of genetic drift since recent founding, maintained by a high degree of endogamy.

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.