Nina Smolej-Narančić

SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout

Uric acid is the end product of purine metabolism in humans and great apes, which have lost hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200–500 μM) compared with other mammals (3–120 μM). About 70% of daily urate disposal occurs via the kidneys, and in 5–25% of the human population, impaired renal excretion leads to hyperuricemia. About 10% of people with hyperuricemia develop gout, an inflammatory arthritis that results from deposition of monosodium urate crystals in the joint. We have identified genetic variants within a transporter gene, SLC2A9, that explain 1.7–5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan in a Croatian population sample. SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in UK, Croatian and German population samples. SLC2A9 is a known fructose transporter, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes.

Inbreeding and risk of late onset complex disease

23 For example, a 4- 5% increase in childhood mortality has been found in the offspring of first cousin marriages, and similar results have been reported in other species. 245 However, the effects of inbreeding on late onset disorders are largely unknown, despite the fact that deleterious effects of inbreeding in other species are known to increase with age, as predicted by selection theory. 67 The reported finding of greater inbreeding effects for traits such as blood pressure and serum cholesterol in middle age compared with early adult life is consistent with this. 8

3000 years of solitude: extreme differentiation in the island isolates of Dalmatia, Croatia

Communities with increased shared ancestry represent invaluable tools for genetic studies of complex traits. ‘1001 Dalmatians’ research program collects biomedical information for genetic epidemiological research from multiple small isolated populations (‘metapopulation’) in the islands of Dalmatia, Croatia. Random samples of 100 individuals from 10 small island settlements (n<2000 inhabitants) were collected in 2002 and 2003. These island communities were carefully chosen to represent a wide range of distinct and well-documented demographic histories. Here, we analysed their genetic make-up using 26 short tandem repeat (STR) markers, at least 5 cM apart. We found a very high level of differentiation between most of these island communities based on Wrights fixation indexes, even within the same island. The model-based clustering algorithm, implemented in STRUCTURE, defined six clusters with very distinct genetic signatures, four of which corresponded to single villages. The extent of background LD, assessed with eight linked markers on Xq13-21, paralleled the extent of differentiation and was also very high in most of the populations under study. For each population, demographic history was characterised and 12 ‘demographic history’ variables were tentatively defined. Following stepwise regression, the demographic history variable that most significantly predicted the extent of LD was the proportion of locally born grandparents. Strong isolation and endogamy are likely to be the main forces maintaining this highly structured overall population.

Prevalence of metabolic syndrome and related metabolic traits in an island population of the Adriatic

Background: Metabolic syndrome, a constellation of risk factors associated with cardiovascular disease and Type 2 diabetes, has reached epidemic proportions worldwide. Epidemiological studies in transitional societies will provide insight into the underlying factors that interact in its manifestation. Aims: To estimate the prevalence of metabolic syndrome, provide a comparative analysis of two metabolic syndrome definitions and assess clustering and association of metabolic traits and cardiovascular diseases in an Adriatic island population. Subjects and methods: In a cross-sectional study, data on four anthropometric, blood pressure and 11 biochemical traits were obtained from 1430 adults from the island of Hvar. Results: Prevalence of metabolic syndrome was 25% and 38.5% based on Adult Treatment Panel III and International Diabetes Federation definitions, respectively. Rates of abdominal obesity, elevated blood glucose and hypertension were high. Among the traits not included in the definitions, levels of LDL, total cholesterol and fibrinogen were markedly elevated. The majority of the phenotypes were significantly associated with the syndrome, the strongest being waist circumference. Conclusion: The Croatian islanders are characterized by a high prevalence of metabolic abnormalities. Central obesity is the strongest contributor of the syndrome. With a high prevalence of dyslipidemia and pro-inflammatory factors, the population is at substantial risk for cardiovascular diseases.

Morphological variation and population structure on the island of Korčula, Yugoslavia

A comparison of head and body morphology on the ecologically uniform island of Korčula provides a good example of the balance that occurs in microevolution between selective pressures toward homogenization and selective inertia toward heterogeneity. thirty-eight measurements were made from a sample of 471 males and 526 females. Head variables, being more eco-stable than body variables, remain relatively more different between two distinct populations (eastern and western villages) than do the more eco-labile body variables, although both do vary significantly between east and west. The differences apply to both men and women. These east-west contrasts reflect the differential migration of Slavs to the island over the past three centuries, with a new wave of immigrants settling mainly in the east and introducing a new gene pool to the pre-existing Slavic hybrid population which had settled the island in the sixth to the eighth centuries. In addition to the predominant east-west differences in morphology, we also find significant variation between all villages in both head and body variables. We conclude that this is an indication of the considerable reproductive isolation that has persisted between all villages until the post-World War II period.

Apolipoprotein H genetic variability in the population of Krk Island, Croatia

Apolipoprotein polymorphisms are emerging as suitable markers for the study of the formation of human populations. In contrast to the data available for apolipoprotein E, the data regarding apolipoprotein H (protein, apoH; gene, APOH) variations are only beginning to accumulate. By blood plasma isoelectric focusing and immunoblotting, we analyzed the distribution of apoH phenotypes in 397 individuals (192 males; 205 females) from seven villages of an autochthonous population of the eastern Adriatic island of Krk. APOH allele frequencies were: APOH*2 = 0.877, APOH*3 = 0.098, APOH*1 = 0.025, with the majority of the sample being homozygous. No significant differences between villages were observed. When these data were compared to those of other populations studied so far, a significant association between APOH allele frequencies and latitude was observed. We hypothesize that this association reflects differences in diet composition across different climatic zones.

Sets of complementary phenotypic relationships across five isolated populations: Traces of expression of different gene complexes?

The aim of this study is to search for certain repeating phenotypic patterns, i.e. sets of complementary relationships across five isolated populations, which may represent the traces of expression of different genes or gene complexes. The study was conducted among isolates of five island populations of eastern Adriatic, Croatia, and the data were collected between 1979 and 1990. Selected phenotypic characteristics included measures of biological distances (e.g. anthropometrical body and head distances, physiological, dermatoglyphic and radiogrammetric bone distances), while other examined traits included sociocultural (linguistic), bio-cultural (migrational kinship) and genetic distances. The sample consisted of 6,286 examinees from 43 villages of five isolate populations. Correlations between distance matrices based on examined traits were analyzed in each of five populations using Mantels test of matrix correspondence, and factor analysis (rotated principal component) was then performed over obtained correlation matrices. The results showed that there were several consistent and significant correlations between some analyzed traits across all of the studied isolate populations, which might indicate their regulation by the shared gene complexes or genome regions. The analyses identified three main clusters of correlations in all five isolate populations: the first one containing anthropometric measures (body and head measures and physiological properties in both sexes), the second one containing geographic distance-related traits (migrational kinship, linguistic and genetic distances), and the third one containing dermatoglyphic properties and radiogrammetric bone measures in both sexes. The higher order varimax rotation over the matrix of factor correlations revealed that the primary source of variation within all five analyzed populations was not sex-related, but rather variable-specific.