Biomedical subjects

Eugene Kobyliansky

Publications and source records attributed to Eugene Kobyliansky.

9 recordsLinked to original sources

PubMed2003

Genetic variation of circulating leptin is involved in genetic variation of hand bone size and geometry.

Leptin is secreted primarily by the adipocytes and plays an important role in the regulation of food intake and energy expenditure. In addition to its adipostatic function, it has been demonstrated that leptin directly enhances stromal cell differentiation to osteoblasts, and since such precursor cells are potential targets for leptin, the latter could possibly mediate the relationship between obesity and bone mass and size. To address this question, we studied phenotypic and genetic correlations between the circulating levels of leptin and hand bone size (BS) and geometry (BG) of the radiographic hand in a healthy and ethnically homogeneous sample of pedigrees. We also attempted to evaluate to what extent potential leptin/BS/BG correlations are modified by an individual's obesity traits, specifically his/her BMI. Our research has shown that leptin, BMI and the corresponding bone measures are clearly inherited traits (0.46+/-0.11, 0.35+/-0.16, 0.62+/-0.12 and 0.51+/-0.09, respectively). The bivariate variance component analysis revealed very strong and significant genetic and environmental correlations between circulating leptin and BMI ( r(G)=0.86+/-0.09, r(E)=0.75+/-0.05, P<0.001). Furthermore, genetic correlations between leptin and hand bone characteristics proved inverse and statistically significant ( r(G)=-0.35+/-0.01 and -0.45+/-0.10 for BS and BG, respectively), while corresponding environmental correlations were low ( r(E)=-0.14+/-0.15 and -0.07+/-0.14) and they could be constrained to zero without significant deterioration of the model fit to the data ( P>0.10). However, despite the extremely strong relationship between leptin and BMI, we failed to detect phenotypic or genetic correlations between BMI and our two hand bone measures. Thus our study provided evidence that plasma leptin levels may be statistically significant predictor of hand bone size and geometry, and may play a physiological role in maintaining bone mass as well as in regulation of hand bone proportions.

Adolescent↗

PubMed2003

Cortical index and size of hand bones: segregation analysis and linkage with the 11q12-13 segment.

BACKGROUND: Bone geometry (BG) and size (BS) are important factors in determining bone fragility. Previous studies have suggested that more than half of BG and BS variation is genetically determined. The possible chromosomal locations of genes involved in BS and BG determination have not been explored. We evaluated the extent and mode of inheritance of the radiographic hand BS index (BSI) and the metacarpal cortical index (MCI), and tested the hypothesis of linkage between these traits and the 11q 12-13 chromosomal region. MATERIAL/METHODS: Hand radiographs and blood samples were collected from 1190 individuals belonging to 349 Chuvasha nuclear families (Russian Federation). Segregation analysis was conducted on a total sample. Transmission disequilibrium testing (TDT) and model-based linkage analyses (MBLA) were performed on a sub-sample of 163 families. RESULTS: The hypothesis of a major gene effect was confirmed for both studied traits. The best-fitting models were Mendelian, with an additive type of inheritance. The inferred major gene explained 50% of the CI and 40% of the BSI variation. The TDT and MBLA results did not permit confirmation of hypotheses about linkage between hand BSI and the 11q 12-13 chromosomal region, but a possible linkage between CI and that region cannot be ruled out. CONCLUSIONS: We support the hypothesis of a major gene effect in the heritability of BSI and MCI. We provide suggestive evidence for possible linkage disequilibrium between MCI and the 11q12-13 chromosomal segment (marker D11S1983), but not for a linkage between BSI and this

Adolescent↗

PubMed2003

Complex segregation analysis of body height, weight and BMI in pedigree data from Middle Dalmatia, Croatia.

It has recently been reported that the mode of inheritance of body height, weight and BMI in five ethnically and geographically different populations can be described in terms of a major gene (MG) model. Here, using the pedigree sample from the island populations of Middle Dalmatia, Croatia (1,312 observed individuals in 462 pedigrees), the evidence is presented that supports the above findings. By applying the usual transmission probability tests, the hypothesis has been accepted that a significant part of the variation of each one of those three basic morphological traits can be attributed to the effect of a putative large-effect gene. The effect of a putative MG is responsible for 39-50% of age and sex adjusted trait's variation and for 34-48% of the total (non age-adjusted) variation of height, weight and BMI.

Adolescent↗

PubMed2002

Genetic and environmental influences on IL-6 and TNF-alpha plasma levels in apparently healthy general population.

Dysregulation of cytokines synthesis is thought to play a role in the development of a number of age-related conditions, such as rheumatoid arthritis, osteoporosis, atherosclerosis, and others, but observational studies have led to contradictory results. We investigated potential familial influences on the plasma levels of IL-6 and TNF-alpha in 91 nuclear and more complex pedigrees of Caucasian ethnic origin (N=401 individuals). The maximum likelihood based variance decomposition analysis showed significant positive correlation between circulating IL-6 and age in both genders. The magnitude of these correlations in our sample ranged from 0.22 in females to 0.28 in males (P<0.001). Significant association between TNF-alpha and IL-6 (r=0.28, r=0.43; P<0.001; respectively for men and women) was also observed. Likelihood ratio test clearly revealed that additive genetic effect for TNF-alpha was highly significant (P<0.001), and accounted over 80% of its variation, adjusted for IL-6 levels and age. In contrast, heritability estimate for IL-6 adjusted for age and TNF-alpha, revealed small contribution of genetic factors (24.1 +/- 10.2%). The bivariate variance component analysis demonstrated that significant relationship between IL-6 and TNF-alpha was due to shared environment only (r(E)=0.760 +/- 0.140). As evinced from our complex segregation analysis the nature of the genetic determinant of each of these two cytokines is quite complex and it is probably oligogenic.

Adult↗

PubMed2002

Pedigree-based quantitative genetic analysis of interindividual variation in circulating levels of IGFBP-3.

Circulating levels of insulin-like growth factor binding protein-3 (IGFBP-3) vary greatly between normal individuals, but until now little attention has been given to the study of the genetic factors involved in IGFBP-3 variability in healthy populations. The present study investigated the extent and pattern of the possible genetic influences on plasma levels of IGFBP-3 in 91 nuclear and more complex families, totaling 396 individuals (201 males and 195 females) of Caucasian ethnic origin. The variance decomposition analysis, was performed using the FISHER statistical package. In the second stage of the analysis, we used complex segregation analysis as implemented in the statistical package MAN. Significant negative correlation was revealed between age and plasma levels of IGFBP-3 in both sexes ( r=-0.49; r=-0.23; P<0.001). Multivariate analysis identified age, body weight, and height as significant covariates in men, but for women only age had a considerable effect. It has been demonstrated that about 57.7% of IGBP-3 variation adjusted for significant confounding factors was attributable to genetic factors. The results of bivariate variance decomposition analysis showed no significant genetic and phenotypic correlation between the mineral density of hand bones and IGFBP-3. Segregation analysis revealed the existence of a potential major gene effect that was able to explain some 27.5% of IGFBP-3 variation. Multifactorial effects, likely, unknown minor genes, contributed an additional 30% to IGFBP-3 variation. The segregation analysis also provided evidence of significant genotype X sex interaction in the determination of plasma levels of IGFBP-3.

Adolescent↗

PubMed2002

Mode of inheritance of hand osteoarthritis in ethnically homogeneous pedigrees.

The aim of the present study was to investigate the extent and mode of inheritance of hand osteoarthritis (OA) using a large sample of ethnically homogeneous pedigrees. Two types of segregation analysis (SA) models were examined. Type I models used the data adjusted for potential significant covariates, particularly age and sex, prior to genetic analysis. Type 11 models incorporated effects of the potential covariates into major gene penetrance functions, permitting an account of the genotype covariate-specific effect on study variables. The results of this study strongly supported the hypothesis of a major gene effect and additional multifactorial component. The best-fitting model was the Mendelian one with an additive type of inheritance. The estimates obtained using the standard three-factor variance decomposition analysis suggest that age (72.8%) and major gene (14.5%) are the main sources of interindividual differences in the development of hand OA. The contribution of the putative major gene on age- and sex-adjusted OA phenotype variation was 55% in the present study.

Adult↗

PubMed2002

Complex segregation analysis of the radiographic phalanges bone mineral density and their age-related changes.

The complex segregation analyses performed in our previous studies revealed a significant major gene (MG) effect on the age-adjusted cortical and cancellous bone mineral density (BMD) in two ethnically different populations, Chuvasha and Turkmenians. The aim of the present study was to test the hypothesis of pleiotropic MG control of three components of bone aging, that is, the baseline level of BMD (mu(gs)), the age at onset of the bone mass loss (T(gs)), and the rate of this loss over the years (alpha(gs)). Nuclear and more complex pedigrees from the same two ethnic samples were assessed for hand phalangeal BMD (Chuvasha, 1208 individuals, and Turkmenians, 643 individuals), and complex segregational analysis incorporating age and sex effects directly into MG penetrance function was carried out. The results of the present analysis clearly confirmed the existence of the putative MG and showed that the proportion of BMD variation attributable to this MG effect within the sex was remarkably similar in both populations and ranged between 34.7% and 35.2%. The most parsimonious model for BMD transmission in Chuvasha pedigrees additionally indicated significant residual correlation between siblings and clear sex differences in the annual rates of bone loss alpha(gs). The latter was more than twice as high in females than that in males (0.086 SD vs. 0.033 SD per year). In Turkmenian pedigrees the most parsimonious model presented obvious evidence of the MG control of BMD baseline levels in both sexes with significantly lower baseline levels and younger age at onset (T(gs)) in females. No clear MG effects were inferred on T(gs) and/or alpha(gs) in either sample, either in males or in females. That is, the present study does not suggest MG x SEX x AGE interaction. We suppose that if the rate of age-related changes in phalangeal BMD is genetically determined, then these are not the same genes as those affecting the BMD baseline levels.

Adolescent↗

PubMed1999

Comparative analysis of age prediction by markers of bone change in the hand assessed by roentgenography.

The major aim of this study was to develop an accurate method of age prediction for a wide range of ages based on the roentgenographic assessment of the hand bones. Such a method may be of particular interest in paleoanthropology and forensic medicine. The present paper provides the results of an analysis of individuals belonging to two ethnically different population samples: 1) Chuvasha (the Russian Federation), 293 males and 254 females, aged 18-91 and 18-86 years, respectively; and 2) Turkmenians (the Republic of Turkmenia), 257 males and 386 females, aged 18-82 and 17-83 years, respectively. The hands of study participants were roentgenographed with standard methodology. For each roentgenogram an equidistant osseographic score (OSS) including the descriptive criteria of bone age was estimated. In addition, an osteoarthritic and an osteoporotic score (OA and OP, respectively) were assigned to each individual. OA was a modification of the Kellgren/Lawrence scale, whereas the OP was locally developed. Results of the multiple logistic regression analysis clearly indicated that OSS is a strong predictor variable of an individual's age, with R reaching 0.93 in Chuvasha and 0.89 in Turkmenians (P < 0.001). The standard errors of estimate were approximately +/-5-7 years and compared favorably with most known methods of age assessment using bones. This study provides an efficient method of age prediction, with acceptable accuracy, and extends the upper limit of prediction to the age of 70 years. An additional finding of interest was the coexistence of OA and OP in the bones of the same hand. The observed correlation between these two conditions reached 0.8 (P < 0.001). Am. J. Hum. Biol. 11:31-43, 1999. Copyright 1999 Wiley-Liss, Inc.

Journal Article↗

PubMedDate not supplied

Interrelationship between bone aging traits and basic anthropometric characteristics.

Using plain hand radiographs, the age dependence of various bone-aging traits (bone mineral density [BMD], cortical index [CI], osteoarthritis [OA], and osseographic [OSS] scores) was evaluated to test whether the correlation among these traits is an individual- or population-based phenomenon. In addition, the effect of anthropometric features on variation of bone-aging traits was estimated. The study included 1,295 individuals from Chuvasha, Russia, 18 to 89 years. BMD was measured from the compact compartment of the middle and distal phalanges of both 3(rd) fingers. The CI of the II-IV metacarpal bones and II-IV proximal phalanges was obtained. The development of OA was based on the standard Kellgren and Lawrence grading scheme for 28 hand joints. OSS score, a surrogate measure that takes into account different kinds of bone changes, was also obtained for each individual. Body weight and height, eight skinfold thicknesses on the trunk and extremities, and breadths of the long bones were measured. Sex-based univariate analyses and multivariate statistical analysis showed the following: 1) Age dependence was defined more strongly in "OA-linked" compared to "osteoporosis (OP)-linked" traits; 2) While "OP-linked" bone-aging traits correlated with age differently between sexes, "OA-linked" traits did not; 3) The strong interrelationship between OA-linked and OP-linked traits in both sexes became very weak and statistically insignificant (P > 0.10) after adjustment for age. Thus, OA and OP conditions in the same individual develop independently and probably reflect different underlying physiological mechanisms. 4) Anthropometric characteristics were significantly correlated with bone-aging traits, but correlations were low (r < 0.20). Thus, the contribution of anthropometric characteristics to the rate and pattern of bone aging of the hand was to relatively small.

Adolescent↗