Screening for nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus using transient elastography - a prospective, cross sectional study.

AIM: To investigate the prevalence and severity of nonalcoholic fatty liver disease (NAFLD) in patients with diabetes mellitus type 2 (T2DM), based on increased controlled attenuation parameter (CAP) and liver stiffness measurements obtained by transient elastography. In addition, we aimed to identify parameters that correlate with increased elastographic parameters of steatosis and fibrosis to provide a better indication when a patient with T2DM should be screened for NAFLD. METHODS: We conducted prospective, cross-sectional study of 679 consecutive adult patients with diagnosed T2DM mean age 65.2±11.6. NAFLD was defined by transient elastography. In 105 patients a percutaneous liver biopsy (LB) was done. RESULTS: The prevalence of NAFLD based on transient elastography was 83.6%. Independent factors associated with increased CAP were higher body mass index, longer T2DM duration, higher serum triglyceride, lower levels of vitamin D, higher C-reactive protein, and higher HOMA-IR. The prevalence of moderate liver fibrosis was 26.9% and advanced liver fibrosis 12.6%. Independent factors associated with moderated fibrosis based on elastography were higher body mass index and higher levels of alanine aminotransferase (ALT), while independent factors associated with advanced fibrosis were female gender, higher body mass index, higher levels of ALT, gama-glutamil transferase and C-reactive protein. Sixty-four (60.9%) of 105 patients with LB had NAFLD activity score ≥5. Regarding the presence and stages of fibrosis based on LB, moderate fibrosis was found in 29.5% of patients, while 29.5% had advanced fibrosis and 6.7% cirrhosis. CONCLUSION: This study supports more aggressive screening for NAFLD and fibrosis in patients with T2DM.

Qualitative dermatoglyphic traits in monozygotic and dizygotic twins of Albanian population in Kosovo.

Dermatoglyphs are polygenetically determined epidermal ridge configurations on the fingers, palms and soles. An analysis of the digito-palmar dermatoglyphics obtained from 69 pairs of same-sex twins (32 monozygotic and 37 dizygotic) was performed in the population of Kosovo. Qualitative traits on the fingers (whorls, arches, radial and ulnar loops) and palms (pattern frequencies in the thenar/I, II, III and IV interdigital areas and hypothenar, the frequencies of positions of axial triradius) of both hands were analysed. The homolateral and heterolateral concordance of dermatoglyphic patterns between twin pairs were calculated for the monozygotic and dizygotic twins separately. The estimates of heritability for qualitative dermatoglyphic traits and the impacts of twin's shared (c(2)) and non-shared (individual) environments (e(2)) were presented. According to our results, the heritability patterns sharply distinguish highly heritable dermatoglyphic traits (patterns on the thenar and I interdigital area, II interdigital area and all the digits) and the traits with weak genetic component (patterns on the III and IV interdigital area, the hypothenar and the axial triradius position). In addition, the concordance and the heritability estimates in twins correspond to the embryonic growth of fingers (from the first to the fifth finger) and palm patterns (the II interdigital area). Based on findings presented here, we expect that the noxious environmental factors (possibly causing diseases later in life) would leave traces on the dermatoglyphs, which could be recognized as the increased dissimilarity of the twins (and other relatives) in the III and IV interdigital area, hypothenar, and in axial triradius position.

The TP53 gene polymorphisms and survival of sporadic breast cancer patients.

The TP53 gene polymorphisms, Arg72Pro and PIN3 (+16 bp), can have prognostic and predictive value in different cancers including breast cancer. The aim of the present study is to investigate a potential association between different genotypes of these polymorphisms and clinicopathological variables with survival of breast cancer patients in Croatian population. Ninety-four women with sporadic breast cancer were retrospectively analyzed. Median follow-up period was 67.9 months. The effects of basic clinical and histopathological characteristics of tumor on survival were tested by Cox's proportional hazards regression analysis. The TNM stage was associated with overall survival by Kaplan-Meier analysis, univariate, and multivariate Cox's proportional hazards regression analysis, while grade was associated with survival by Kaplan-Meier analysis and univariate Cox's proportional hazards regression analysis. Different genotypes of the Arg72Pro and PIN3 (+16 bp) polymorphisms had no significant impact on survival in breast cancer patients. However, in subgroup of patients treated with chemotherapy without anthracycline, the A2A2 genotype of the PIN3 (+16 bp) polymorphism was associated with poorer overall survival than other genotypes by Kaplan-Meier analysis (P = 0.048). The TP53 polymorphisms, Arg72Pro and PIN3 (+16 bp), had no impact on survival in unselected sporadic breast cancer patients in Croatian population. However, the results support the role of the A2A2 genotype of the PIN3 (+16 bp) polymorphism as a marker for identification of patients that may benefit from anthracycline-containing chemotherapy.

TP53 gene polymorphisms and breast cancer in Croatian women: a pilot study.

A case-control retrospective association study was conducted to investigate a possible association of the TP53 polymorphisms, Arg72Pro and PIN3 (+16bp), with sporadic breast cancer in Croatian women. Ninety-five women with breast cancer and 108 age-matched healthy women were analyzed. Arg72Pro polymorphism was detected by TaqMan essay. For designation of PIN3 (+16bp) polymorphism DNA amplification was performed by the polymerase chain reaction (PCR) while the PCR products were detected by capillary electrophoresis. Homozygous genotype of minor allele of the PIN3 (+16bp) polymorphism was associated with sporadic breast cancer (OR = 2.15, 95% confidence interval [CI] 1.80-2.56, p = 0.006). For Arg72 polymorphism, the odds ratio for breast cancer of ArgPro versus reference genotype ArgArg was 0.55 (95% CI 0.30-1.02, p = 0.039) suggesting the protective effect. Although different haplotypes did not influence the susceptibility to the disease, the joint occurrence of genotype combination ProPro/A2A2 frequent in cases, was associated with sporadic breast cancer (OR = 2.20, 95% CI 1.89-2.56, p = 0.021). The study provides evidence of the association of the TP53 gene polymorphisms Arg72Pro and PIN3 (+16bp) with sporadic breast cancer in the Croatian population.

Evidence on major gene control of cortical index in pedigree data from Middle Dalmatia, Croatia.

It was recently reported that the inheritance of the metacarpal cortical index (CI) in the Chuvashian population can be described in terms of a major gene (MG) model. By applying transmission probability tests, the hypothesis was accepted that not only baseline level of CI but also its sex-specific dependence on age were under control of the same putative large-effect gene. Using a pedigree sample from the population of the islands of Middle Dalmatia, Croatia (847 observed individuals in 278 pedigrees), data are presented to support the above findings. The following hypotheses were accepted: (i) inheritance of baseline CI in the Croatian population can be attributed to the effect of a MG responsible for about 42% of the variation; (ii) the same MG takes part in the control of the dependence of CI on age, particularly the age at onset of involutive bone changes (inflection point), and of the rate of decrease in CI with age (slope coefficient). Issues related to the assortative mating effect on CI and the determination of the most parsimonious model are discussed.

Vertebral artery hypoplasia--sex-specific frequencies in 36 parent-offspring pairs.

The major interest in vertebral artery (VA) hypoplasia comes from its possible connection to migraines with aura as well as from the fact that it is one of the risk factors for a stroke. Therefore, the aim of this preliminary study was to investigate the mode of inheritance of VA hypoplasia. Initially, color Doppler of VA was performed in 64 first- and second-degree relatives of 33 probands, and the presence of VA hypoplasia was confirmed according to the already established criteria. Since a higher prevalence of VA hypoplasia (15.6%) in probands'relatives in comparison with 2.34% in the general population of Croatia was indicative of a strong familial predisposition for this condition, an analysis of family data by means of Pearson's chi-square statistics has been performed. In this analysis, the observed sex-specific frequencies of 36 parent-offspring pairs composed only of affected parent and his/her (affected or non-affected) offspring are compared to the frequencies as expected under eight proposed models. For both--autosomal and X-linked monogenetic inheritance--four hypotheses have been chosen, assuming that the individuals having the affected allele (in combination with a healthy one) have 100%, 50%, 40% and 0% chances of developing VA hypoplasia. Out of eight tested models only two--completely dominant and completely recessive X-linked models--were rejected. But, from the six non-rejected models, goodness-of-fit statistics showed that the hypothesis of X-linked inheritance of VA hypoplasia with the "healthy" allele being stronger (60% effect on phenotype)--almost perfectly fit the data (chi2 = 2.0023; df = 7; p = 0.9597). Further research encompassing a more enlarged family sample is needed to confirm the present findings.

The analysis of population structure based on morphometric dimensions of metacarpal bones (the Island of Krk, Croatia).

The aim of this study was to investigate: 1) a possibility of using the morphometric dimensions of metacarpal bones for approximation of biological distances, and 2) a relationship of biological matrices, based on the morphometric dimensions of metacarpal bones to other biological (dermatoglyphic, genetic), bio-cultural (migration) and geographic variables. The morphometry of the metacarpal bones was performed according to Barnett and Nordin procedure and biological distances were estimated using Mahalanobis D2 method. Population structure was assessed through Mantel's permutation test using E2 genetic distances for classical serogenetic markers, DA genetic distances for HLA, DSW genetic distances for STRs, geographic distances expressed in kilometres, and migration kinship matrix estimated according to the method proposed by Malécot and modified by Morton. This study clearly indicated the need for applying factorial analytical approach to study the factor structure of morphometric variables that may be measured on six metacarpal bones as well as the need for conducting complex family and segregation analyses to address not only the intriguing issue of genetic vs. ecological impact onto the bone mineral turnover, but also to test the hypothesis of major gene control in determining bone mineral density.

Osteometric dimensions of metacarpal bones with respect to the professional exposure to vibration.

The comparative analysis of the osteometric dimensions of metacarpal bones in three groups of males (aged from 23 to 63 years) differing with respect to the presence of the professionally connected long-term exposure to the vibration is performed. The sample encompasses forest workers employed in wood industry (exposed to heavy physical work and to the daily use of hand-held vibrating tools) from two regions of Croatia: Podravina (n = 192) and Gorski Kotar (n = 115). The control group is formed using the random sample (selected according to age criterion) of phenotypically healthy male inhabitants of rural communities of Eastern Adriatic islands and peninsula (n = 200). Additionally, the influence of the level of calcium in diet, as a regional nutritional characteristic of particular regions of Croatia, is also considered. The regression of the percent cortical area (PCA) of the second left metacarpal bone and age showed that significant decrease of PCA in older age can be observed only in males from Eastern Adriatic (the control group), while that is not so in either group of males professionally exposed to vibration. Authors conclude that the analysis of the osteometric dimensions performed on males professionally daily exposed to vibration missed to provide evidence to support the hypothesis of long-term exposure to vibration as a risk for accelerated osteoporosis of metacarpal bones.

Morphometric dimensions of metacarpal bones in the population structure analysis (island of Krk, Croatia).

The population structure analysis by means of the osteometric dimensions of metacarpal bones in the population groups of the northern Adriatic island of Krk, Croatia was performed. The sample consisted of randomly sampled adult islanders (94 males and 79 females) aged from 18 to 85 years from six villages of the island of Krk. "Biological distances" were estimated by the Mahalanobis D2 analysis for bone length (L), total diaphysis width (T) and medullary canal width (M) dimensions of the second left metacarpal bone. Analysis of the osteometric dimensions of metacarpal bones as a measure of biological distance between population groups of the island of Krk indicated bio-cultural and socio-cultural events, rather than geographical distances, to be the primary determinants of anthropogenetic structure of today's population groups of the island.

Family correlations of metacarpal bones--heritable (h2) and environmental (c2) components of total phenotypic variation.

The analysis of family data of 18 metacarpal morphometric dimensions (bone length -L, total diaphysis width-T and medullary canal width-M of the second, third and fourth metacarpals of both hands) has been performed on 956 randomly sampled adult examinees (age 18 to 85), inhabitants of the islands of Brac and Hvar and the Peljesac peninsula, Croatia. Interclass (for parent-offspring family pairs) and intraclass (for siblings) correlation coefficients have been calculated as well as heritability coefficient (h2) and coefficient quantifying effects of common sibling environment (c2) have been estimated. Heritability estimates (h2) for the medullary canal width dimensions (54%-71%) showed to be at least as high, and c2 (2%-14%) values showed to be at least as low as those obtained for bone length dimensions (h2 = 51%-65%; c2 = 5%-16%) suggesting a strong influence of genetic factors in medullary canal width formation. For both traits the highest heritability and the lowest environmental component is found for dimensions of 4th metacarpal bone, which could be explained by lower biomechanical pressures acting on that bone owing to it's anatomical position. Analysis of family resemblance for medullary canal width showed the tendency of female family pair (Mother-daughter) to be less correlated than other family pairs, which is especially pronounced in fourth metacarpals. We assume that lower correlation values of Mother-daughter pair can be the result of non-linearity of age dependent changes in medullary canal width dimensions associated with the osteoporotic process which is more active in females. Clearly lower heritability values obtained for total diaphysis width dimensions (25%-48%) and higher values obtained for c2 (14%-23%), in addition to findings of higher correlation values in same sex family pairs (Father-son, Mother-daughter) speaks in favor of substantial importance of common family environmental factors--particularly sexually specific physical activity--which through the short-term adaptation processes modify the total diaphysis width dimension phenotype.