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A Chuvashian population-based sample included 802 males and 738 females (mean age 46.98±17.10 and 48.65±16.62 years, correspondingly). Age, basic demographics, anthropometric data, reproductive indices, and x-rays of both hands were collected. Results and discussion. Familial correlations of FLR traits showed no significant correlation for spouses, however, parent-offspring (0.15-0.28, p

The aim of this work was to study taste sensitivity to phenylthiocarbamide (PTC) amongst Bedouin tribes and compare the Bedouins with Arab and Jewish populations. Data obtained by the classic method of serial dilutions in 317 healthy male Bedouins, aged 16–70 belonging to different tribes, were examined. We discovered significant differ­ences in chemosensitivity to PTC in the Bedouin communities. A high frequency of the t allele was documented in the Bedouin tribes of Hamada, Muzeina, and “other Bedouins” and a relatively low level of the t allele frequency in the Gebelia tribe. The frequencies of non-tasters amongst Arab groups were similar in values to those of the Gebelia tribe. Three other Bedouin tribes showed very high values for the non-tasters’ frequencies. The revealed intertribal differ­ences can be explained by the genetic drift in isolated populations, on the other hand, this may be the result of endog­amy. DOI https://doi.org/10.5671/ca.45.1.3

This study aimed to evaluate the association between the index to ring (2D:4D) finger length ratio and aging-related traits (hand osteoarthritis (OA), the osseographic score (OSS), and reproductive period), as well as to assess the heritability of finger length. A Chuvashian population-based sample included 802 males (mean age 46.98±17.10 years) and 738 females (mean age 48.65±16.62 years). Age, sex, basic demographics, anthropometric data, reproductive indices (age at menarche, menopausal age, and length of the reproductive period), and x-rays of both hands were collected. Finger length ratio was measured on x-ray and each hand was visually classified as either type 1 – 2D>4D; type 2 ― 2D=4D; or type 3 ― 2D

The long term skeletal effects of antenatal exposure to teratogen 5-deoxy-2′-cytidine (5-AZA) were studied using two inbred strains, C3H/HeJ (C3H, with inherently stronger bones) and C57Bl/6J (C57, with weaker bones). We previously reported that in-utero exposure to 5-AZA resulted in loss of bone quality in 3- and 6-mo-old C3H offspring. In this study, we further examined whether the long-term effects of an acute teratogenic exposure are still evident in older mice. Bone phenotypes of 12 mo-old mice exposed to a single injection of 5-AZA on day 10 of their mother's pregnancy were evaluated by micro-computed tomography and compared to the untreated controls.The main observation of this study is that 5-AZA-induced loss of bone length was registered in 12-mo-old C57 and C3H males. As expected, we did not find differences in the 3rd lumbar vertebra since in-utero exposure to 5-AZA was shown to affect the limb buds but not the axial skeleton. Trajectory of changes in bone phenotypes from ages 3 mo through 6 mo to 12 mo was also compared; 5-AZA-exposed C57 males had consistently lower femoral length and trabecular BMD than age-matched controls. In summary, by characterizing teratogen-exposed C57 and C3H mice, we further confirmed that the adaptive response to antenatal insults continue into mid-life of the mice as well as there is a sex-specificity of these responses. Keywords: Bone loss, Genetic heterogeneity, Adult mice, Developmental origin of diseases

OBJECTIVES The purpose of this study was to compare the prevalence of finger length ratio between three longevity populations (Abkhazians, Azerbaijanis, and Georgians) and one nonlongevity population (Russians), as well as between a longevity and nonlongevity sample within one ethnic group (Abkhazians). METHODS In a cross-sectional observational study, we compared the prevalence of finger length ratio in longevity vs nonlongevity samples. RESULTS A negative relationship was observed between longevity index and prevalence of type 1 (feminine type) ratio. In longevity samples, the prevalence of type 1 ratio was lower and the prevalence of type 3 (masculine type) ratio was higher than in the nonlongevity sample of Russians. This difference was statistically significant (P

In this study we examined to what extent and how genetics may modify osteoporosis risk arising due to environmental stresses which act during the antenatal period of life and have the potential to induce bone loss in adulthood. C57Bl/6J (C57) and C3H/HeJ (C3H) mice were used as a model system. The mice were exposed to a single injection of 5-aza-2'-deoxycytidine (5-AZA) on day 10 of pregnancy and the structure and bone mineral density (BMD) of the femur and 3rd lumbar vertebra of 3- and 6-month-old male and female offspring were evaluated by micro-computed tomography (μCT). Besides, we also attempted to evaluate whether 5-AZA affects the expression of some osteogenic genes in the embryonic limb buds. The main observation of this study is that 5-AZA-induced loss of bone quality was registered in 6-mo-old C3H offspring but not in their C57 counterparts. We also observed that C57 and C3H embryos may differ in their response to 5-AZA-induced detrimental stimuli: whereas 5-AZA treated C3H embryos exhibited a decreased expression of Col1a1, C57 embryos exhibit a decreased expression of Sox9. Overall, our study, by thorough characterization of bone homeostasis in 3- and 6-month-old offspring of 5-AZA-exposed C57 and C3H mice, allows hypothesizing that the adaptive response to antenatal insults may be stronger in offspring inherently exhibiting a low bone mass phenotype than in offspring inherently exhibiting a high bone mass phenotype.

OBJECTIVES The purpose of this study was to evaluate the familial correlations and heritability of 2D:4D ratio traits using a large population-based sample of ethnically homogeneous pedigrees from Chuvasha and Bashkortostan Autonomies of the Russian Federation. METHODS We calculated the familial correlations and performed a heritability analysis of 2D:4D ratio traits in a sample of 1541 subjects (803 men and 738 women, mean age 47.78 ± 16.89 years, range 18-90 years). RESULTS Familial correlations of 2D:4D ratio traits showed no significant correlation for spouses; however, parent-offspring (0.15-0.28, P

The aim of this population-based study was to evaluate the association between the index to ring (2D:4D) finger length ratio and the osseographic score (OSS), the skeletal biomarker of biological aging. A sample included 802 males and 738 females who had participated in a Chuvashian skeletal aging study. Age, sex, basic demographics, anthropometric data and X-rays of both hands were collected. Each hand was visually classified on X-ray as either Type 1 - index finger was longer than ring finger; Type 2 - equal; or Type 3 - shorter than the ring finger. OSS is a skeletal biomarker that comprises osteoporotic and osteoarthritic changes observable on a hands X-ray. The mean age of males in the studies sample was 46.98 ± 17.10 and mean age females was 48.65 ± 16.62. OSS showed significant association with age (r = 0.886, p < 0.001), body mass index (BMI) (r-0.253, p < 0.001) and sex (F = 13.771, p < 0.001). Results of one-way ANCOVA for finger length ratio types of right hand showed a significant difference in OSS (d.f. = 2, F = 7.569, p = 0.001), after adjustment for age, sex, and BMI. The posthoc comparison showed that individuals with Type 3 (2D < 4D) ratio showed significantly higher OSS scores that ones with Type 1 (p = 0.012) and Type 2 (p = 0.003). In an analysis of finger length ratio types of left hand also a significant difference in OSS was found (d.f. = 2, F = 3.290, p = 0.038). The posthoc comparison showed that individuals with Type 3 (2D < 4D) ratio showed significantly higher OSS scores that ones with Type 2 (p = 0.33) ratio. Finger length ratio is associated with an OSS, a skeletal biomarker of biological aging. Individuals with Type 3 finger length pattern showed significantly higher OSS that ones with Type 1 and Type 2.

Age-related changes in hand bones were studied in adult urban dwellers of Eastern Europe (Lithuania, Komi, and Moscow), and in first- and second- generation migrants from European countries to Israel, compared with the indigenous population of the Middle East. The total sample size was 1828. Signs of aging in the shape and structure of hand bones were assessed with x-rays using the OSSEO method. The results indicate a moderate level of adaptation discomfort, which is more pronounced in oilfield workers in Ukhta and in Moscow females. The aging of skeletal bones was more rapid in the migrant Israeli population of Kfar Saba than in the indigenous population of the Middle East. The results of the osseographic analysis support the hypothesis of adaptive stress in modern urban and migrant populations.

Objective to evaluate the association between 2D:4D finger length ratios (representing the prenatal environment, i.e., early androgen exposure) and reproductive indices, such as age at menarche, menopausal age, and length of reproductive period. Methods Retrospective data on age at menarche and menopausal age as well as x-rays of both hands were obtained from 674 Chuvashian women aged 18–70 years (mean 46.32 ± 15.42). Finger and metacarpal length ratios as well as visual classification of finger ratio types, were estimated from the x-rays. Results and Conclusions We found that a low 2D:4D ratio (radiologically evaluated), a masculine 2D:4D ratio type (visually evaluated), and a putative bioassay for prenatal androgen exposure, were associated with a later menarche and a shorter reproductive period. No association was found with menopausal age. Am. J. Hum. Biol. 25:617–621, 2013. © 2013 Wiley Periodicals, Inc.

In a sample of Chuvashians (803 males and 738 females) we evaluated the mean values of index finger to ring finger (2D:4D) ratio, the contributions of phalanges and metacarpals to the 2D:4D ratio, and the symmetry between right and left 2D:4D ratios. Age, sex, anthropometric data and radiographs of both hands were collected. Each hand was visually classified on a radiograph as either Type 1 - index finger was longer than ring finger; Type 2 - equal; or Type 3 - index shorter than the ring finger. The following measurements (1) from the mid-point of the base of the proximal phalanx to the mid-point of the tip of the distal phalanx; and (2) from the mid-point of the base to the mid-point of the tip of the metacarpal were obtained from the index and ring fingers. Visual classification was significantly associated with the measured 2D:4D length ratio. Women had a higher prevalence of Type 1 and Type 2, but lower prevalence of Type 3 ratio in both hands. Men had smaller measured 2D:4D phalangeal, metacarpal and ray (combined) ratios than women. Symmetry between the right and left hand measured 2D:4D ratios were significant in phalangeal (r=0.657, p0.001), metacarpal (r=0.638, p0.001), ray (r=0.682, p0.001) ratios and visual classification types (contingency coefficient=0.559, p0.001). No sex dimorphism was found between the right and left hands. Correlations between age and visual classification were significant on both sides before and after adjustment for sex. This result is probably a sign of a secular trend in the Chuvashian sample and the study should be replicated in other samples.

BACKGROUND To our knowledge, there are no experimental studies that have addressed the effects of starvation on the maintenance of telomere length. Two epidemiologic studies that have addressed this topic gave controversial results. OBJECTIVE We characterized leukocyte telomere length (LTL) in a Chuvash population that was comprised of survivors of the mass famine of 1922-1923 and in these survivors' descendants. DESIGN The tested cohort consisted of native Chuvash men (n = 687) and women (n = 647) who were born between 1909 and 1980 and who resided in small villages in the Chuvash Republic of the Russian Federation. Data were gathered during 3 expeditions undertaken in 1994, 1999, and 2002. With the use of this method of gathering the study cohort, we were able to treat age and birth year as independent variables (i.e., after adjustment for age, we were able to analyze how LTL correlates with a birth year in the interval between 1909 and 1980). The DNA of peripheral blood leukocytes was used to measure the telomere length with a quantitative polymerase chain reaction technique. RESULTS The main observations were as follows: 1) there were shorter leukocyte telomeres in men born after 1923 (i.e., after the mass famine) than in men born before 1922 (i.e., before the mass famine); 2) there was a stable inheritance of shorter telomeres by men of ensuing generations; and 3) there was an absence of a correlation between LTL and birth year in women. CONCLUSIONS Our study does not provide direct evidence for leukocyte telomere shortening in famine survivors. However, the comparative analysis of LTL in the survivors and their descendants suggests that such an effect did take place. The study also implies that mass famine may be associated with telomere shortening in male descendants of famine survivors. This observation is in agreement with the "thrifty telomere hypothesis" predicting that longer telomeres are disadvantageous in nutritionally marginal environments.

Dermatoglyphic traits in a sample of twins were analyzed to estimate the resemblance between MZ and DZ twins and to evaluate the mode of inheritance by using the maximum likelihood-based Variance decomposition analysis. The additive genetic variance component was significant in both sexes for four traits--PII, AB_RC, RC_HB, and ATD_L. AB RC and RC_HB had significant sex differences in means, whereas PII and ATD_L did not. The results of the Bivariate Variance decomposition analysis revealed that PII and RC_HB have a significant correlation in both genetic and residual components. Significant correlation in the additive genetic variance between AB_RC and ATD_L was observed. The same analysis only for the females sub-sample in the three traits RBL, RBR and AB_DIS shows that the additive genetic RBR component was significant and the AB_DIS sibling component was not significant while others cannot be constrained to zero. The additive variance for AB DIS sibling component was not significant. The three components additive, sibling and residual were significantly correlated between each pair of traits revealed by the Bivariate Variance decomposition analysis.

Previous studies have reported that centenarians escape the major agerelated diseases. No studies on prevalence and severity of osteoarthritis (OA) in longevity population have previously been reported. Because OA is associated with morbidity and mortality, we hypothesized that radiographic hand OA would generally be less prevalent and would develop at a later age in longevity populations vs non-longevity populations. Aim was to evaluate the prevalence and mode of development of radiographic hand OA in three longevity populations (Abkhazians, Azerbaijanis and Georgians) and in one non-longevity population (Russians).Crosssectional observational study. Longevity index was calculated as a ratio of the number of individuals aged90 years vs the number of people aged60, expressed per mil (‰). A population with longevity index40‰was considered as a longevity population. Radiographic hand OA was evaluated using the left hand radiograms in 14 joints according to Kellgren and Lawrence's (K-L) grading system. Each individual was characterized by the total number of affected (K-L≥2) joints (NAJ). Prevalence of hand OA was defined as the presence of at least one affected joint. Statistical analyses included prevalence estimation, linear, logistic and polynomial regressions, and ANOVA.A significant difference (p0.003) in age standardized prevalence of hand OA was found between each pair of studied samples, except between Russians and Georgians and between Azerbaijanis and Abkhazians (p0.05). The lowest age-standardized prevalence was found in Abkhazians, followed by Azerbaijanis and Georgians. The highest prevalence was found in Russians. ANOVA showed significant differences (p0.01) between the age-adjusted means of NAJs. The lowest age-adjusted NAJ was found in the Abkhazian population, followed by Azerbaijanis and Georgians. The highest NAJ was found in Russians.We observed that the pattern of radiographic hand OA in longevity populations differs from the pattern in non-longevity populations. On average, first joints with OA appear at an older age, and progression of hand OA, measured by NAJ, is slower.

18 quantitative finger and palmar dermatoglyphic traits were analyzed with the aim of determining genetic effects and common familial environmental influences on a large (358 nuclear pedigrees) number of twins (MZ and DZ). Genetic analysis based on principal factors includes variance and bivariate variance decomposition analysis. Especially, Factor 1 (digital pattern size) is remarkable, due to its degree of universality. The results of genetic analysis revealed all three extracted factors have significant proportion of additive genetic variance (93.5 % to 72.9 %). The main results of bivariate variance decomposition analysis appears significant correlation in residual variance between digital pattern size factor (Factor 1) versus finger pattern intensity factor (Factor 4), and palmar main lines factor (Factor 2) verses a-b ridge count (Factor 3), but there was no significant correlation in the genetic variance of factors.

The objective of this study is to evaluate the association between radiographic hand osteoarthritis and serum level of osteocalcin. The study population comprised Chuvashians (285 males, age 47.38 +/- 16.79; 265 females, age 48.55 +/- 15.94 years). OA was evaluated for 14 joints of each hand using Kellgren and Lawrence (K-L), joint space narrowing (JSN) and osteophytes (OS) scores. Plasma-intact osteocalcin was measured in 550 individuals by immunoradiometric assay using ELSA-OSTEO kit. Statistical analyses included multiple linear and logistic regressions. 51.64% of studied individuals had at least one finger joint affected at K-L > or = 2 level. JSN at the level > or = 2 was found in 9.82% and OS > or = 2 was found in 35.09% of the studied individuals. Osteocalcin showed a modest, but statistically significant, association with the number of affected joints according the K-L scale (beta = 0.082, p = 0.015), JSN scale (beta = 0.097, p = 0.025) and OS scale (beta = 0.078, p = 0.029). No significant association was found between the presence of at least one affected joint (K-L > or = 2 or OS > or = 2) and serum level of osteocalcin. Presence of at least one joint with space narrowing > or = 2 was significantly associated with serum level of osteocalcin (beta = 0.052, p = 0.023). In this cross-sectional population-based study, we found that serum level of osteocalcin is positively associated with severity of hand OA, measured by K-L, JSN and OS scales.

The aim of the study was to evaluate the prevalence and pattern of radiographic hand osteoarthritis (OA) in an Abkhazian community-based sample and its association with age, sex, body mass index (BMI) and place of residence. The study sample was comprised of 542 males with a mean age of 43.9, sd 15.6 years and 463 females with a mean age of 44.9, sd 13.9 years. OA was evaluated for 14 joints of the left hand according to the Kellgren and Lawrence grading scheme. Statistical analyses included prevalence estimation, multiple regression analysis and chi(2) tests. In the entire Abkhazian sample the average prevalence of hand OA was 33.6% for males and 35.4% for females. After age 65, the prevalence of hand OA was 87.5% for males and 83.3% for females. No sex differences were found in the prevalence or number of affected hand joints. Statistically significant association was found between the number of affected joints and BMI, but not between the prevalence of hand OA and BMI. Different prevalences of radiographic hand OA were found in individuals from different villages, after adjustment for age, sex and BMI. Additional studies are needed to explore the possible reasons for such differences.

SUMMARY Objective of this study is to explore the nature of sex differences between two different sets of dermatoglyphic traits based on principal components in the Turkmenian population. Two categories of dermatoglyphic traits--22 usually studied quantitative traits and 42 variables of diversity and asymmetry were analysed among 745 individuals (309 males and 436 females). The three principal components are very prominent in both sexes--"digital pattern size factor" indicates the degree of universality, as found in earlier studies among different ethnic populations; "intra individual diversity factor" and "bilateral asymmetry factor" are also similar with the earlier studies, which suggest the genetic factor has more influence on these variables than environmental factors. These results strongly indicate that there is a common biological validity exists of the underlying principal component structures between two different sets of dermatoglyphic characters and thus dermatoglyphic factors between two groups of variables can be used for sex-discrimination in different populations.

Serological and biochemical polymorphisms in marker genes of the AB0, MN, RH, FY, HP, TF, ACP1, PGM1, ESD, and GLO1 systems were studied in the combined sample of 369 individuals of Chuvash ethnicity from Morgaushskii, Mariinsko-Posadskii and Yadrinskii districts of the Chuvash Republic. We have compared our results with the data obtained in previous studies by other authors. A linear relationship has been established between genetic and geographical distances by examining 11 ethnoterritorial groups in Northeastern Europe and Western Siberia.

The main goal of the present communication is to determine the mode of inheritance of dermatoglyphic diversity traits through complex segregation analyses (genetic model fittings). The data consists of a large ethnically homogeneous sample of 500 Indian pedigrees (2435 individuals) of two generations. Principal component analysis, familial correlations and segregation analysis (package MAN-5) were used. A little genetic effect obtained from familial correlations but no evidence of major gene contribution found to be involved. By segregation analysis of the traits- PC 1_ Div, Div 9 and Div 11, both Mendelian and Environmental models were rejected (<

Adipokines may link adipose tissue to the inflammatory, metabolic, and immune dysregulation. The variation of adipokine levels within individuals, intercorrelations, and relationships to well-established measures of adiposity are incompletely defined. The main goal of the present study was quantitative evaluation of the genetic interrelationships between obesity and adipokines in normal human population. The study sample comprised 272 families of various sizes, including 530 men and 531 women aged 18-80 years, randomly recruited in rural population living in Russia. Various fatness and fat distribution measures (OB), blood pressure (BP), and plasma levels of several adipokines (AC), such as adiponectin, leptin, resistin, and IGFBP-1, have been measured. The likelihood ratio tests clearly revealed that genetic effect for all studied phenotypes was highly significant (P < 0.001) and accounted for 45.9% +/- 8.1%, 33.7% +/- 7.9%, 35.7% +/- 9.8% of variation for AC, OB, and BP, respectively. The pairwise bivariate analyses showed that strong phenotypic correlation between the obesity (OB) and adipocytokines (AC) was caused by both common genetic and environmental factors (r(G) = 0.597 +/- 0.116, r(E) = 0.671 +/- 0.051). The phenotypic correlation between BP and OB is explained by shared genetic factors only (r(G) = 0.532 +/- 0.109), whereas the phenotypic correlation between BP and AC has only common environment basis (r(E) = -0.212 +/- 0.081) and was mostly due to the correlation observed in females. Our results suggest that genetic factors play a significant role in regulation of variation of the examined traits. The variation of OB traits is almost fully due to genes influencing variation of AC, whereas the correlation between BP and AC is only marginally significant and caused only by shared environment.

The aim of the study was to evaluate the prevalence and pattern of radiographic hand osteoarthritis (OA) in Turkmen community-based sample and its association with age, sex, and BMI. The study population was comprised of Turkmens (277 males and 427 females, age 19–90 years). OA was evaluated for 14 joints of each hand according to the Kellgren and Lawrence grading scheme. Statistical analyses included prevalence estimation, linear and polynomial regressions, and χ 2 tests. About 13.8% of individuals before age 36 had at least one joint with OA, and the prevalence reached 100% after age 65. For males and females the best-fitted and most parsimonious model of association between age and number of affected hand joints was a two interval linear one. After adjustment for age, we found that females with severe obesity have higher risk of development of hand OA than those with normal weight [OR(95%CI): 3.88 (1.20–12.60)].

Objective: Several previous studies support the association between manual dominance and age at menarche or age at menopause. The aim of the present study was to estimate the association between indices of laterality and reproductive indices. Design: The studied sample comprised 650 Chuvashian women aged 18 to 80 years (mean, 46.9; SD = 16.2). The independent-sample t test was used to compare the age at menarche or age at menopause between individuals with right or left dominance of handedness, dominant eye, hand clasping, and arm folding. Results: No significant differences in age at menarche or age at menopause between women with right and left dominance in any of the studied laterality indices were found. Conclusions: This is the first study that simultaneously evaluates the association between dominance in four laterality indices (handedness, dominant eye, hand clasping, and arm folding) and two reproductive indices (age at menarche and age at menopause). Result of our study do not support the hypothesis of a possible association between handedness (and other indices of laterality) and an early age at menarche or age at natural menopause.

The aim of the present study was to evaluate age- and sex-related changes in the size and shape of long hand bones in a large Chuvashian cohort using cross-sectional and longitudinal study designs. The data were gathered in 1994 (557 individuals) and 2002 (513 individuals). The latter sample included 260 individuals that were studied only during the second expedition, and 253 individuals who were previously investigated in 1994. Statistical analyses included a maximum likelihood-based model-fitting technique and a t-test comparison. We found evidence for secular trend of hand bone size in both males and females within the Chuvashian population. In males, the length and total area of the long hand bones were greater in younger individuals, but mid-shaft bone width remained almost the same in individuals born at different periods of the last century. In females, the length of the hand bones and total bone area remained unchanged in women born after 1937. However, bone mid-shaft width gradually decreased in women born after 1940. Therefore, we argue that, at least within the Chuvashian population, there is a secular trend towards a more gracile appendicular skeleton in both males and females.

With the aim of determining sex dimorphism among the Chuvashian population of Russia, digital and palmar dermatoglyphics of 547 individuals (293 males, 254 females) were analyzed. The sex differences for PII, TRC, and AFRC are similar to Indian and Jewish populations. Correlation coefficients between individual finger ridge counts are a little lower than in Jews but are almost equal to Indian populations. The Mantel test of matrix correlation between sexes for 22 traits shows a very good similarity. However, sex differences of palmar traits display different levels when compared with other human populations. In light of this, our evidence indicates the possible role of environmental (prenatal) factors in the realization of dermatoglyphic sex differences. The development of palmar dermatoglyphics has had a relatively longer growth period compared with fingers [Cummins, H., 1929. The topographic history of the volar pads (walking pads, tast ballen) in the human embryo. Embryol. 20, 103-126]. The palmar dermatoglyphic pattern of affinities therefore corresponds better than fingers to the ethno historical background of the populations, ascertained by numerous studies.

Summary Osteoporosis is characterized by reduced bone strength. Bone size and bone mineral density (BMD) are major bone strength determinants. Identification of genes affecting the variability of these traits should improve prognosis and management of osteoporosis. This research was aimed to test the hypothesis of association of radiographic hand bone length (BL) and BMD with polymorphisms in the RUNX2 locus. Four SNPs linked to the two RUNX2 promoters were genotyped in 212 nuclear Caucasian families. These SNPs and four pairwise haplotypes were tested for association with eight BL and BMD traits, adjusted for covariates. We observed significant associations between polymorphisms linked to the RUNX2 P1 promoter and BL mean values for three studied bone groups: all 18 bones, proximal and medial bones (p = 0.0118, 0.0085, and 0.0056, respectively). Mean BMD values for all 18 bones, proximal and medial bones were associated with polymorphisms linked to the RUNX2 P2 promoter (p = 0.0032, 0.0077, 0.0007, respectively). Associations with BL and BMD mean values for medial and proximal bones remained significant even after correction for multiple testing. This study provides evidence of the association between polymorphisms linked to the two RUNX2 promoters and variability of hand BL and BMD. The results suggest independent roles for the two RUNX2 promoters in the determination of the traits studied.

Summary Objectives Previous studies showed increased femoral, neck, and tibial plateau with age in individuals with and without osteoarthritis (OA) at adjacent joints. However, the question whether epiphyseal bone enlargement is a natural phenomenon of aging or associated with OA remains open. The aim of the present study was to evaluate age- and sex-related changes in the relative size of epiphyses of long hand bones and their association with radiographic OA. Design The data were collected from a population-based European sample in 1994 (557 individuals) and in 2002 (513 individuals). The latter sample included 253 individuals who were previously investigated in 1994. The epiphyseal index (EI), reflecting the relative size of bone epiphyses and hand OA, was evaluated from hand radiographs. Statistical analyses included multiple regression analyses and a maximum likelihood-based model-fitting technique. Results Hand bone epiphyses increased with age and with OA. In males, the EI gradually increased during their entire life span. In females, the EI remained almost unchanged up to the age of 40, after which, it increased more rapidly than in males. Individuals with OA had higher values of EI at any age. In both sexes, epiphyseal enlargement is a predisposing factor for hand OA progression in adjacent joints. This was clearly seen in males, where old individuals with high EI values had much higher OA scores in comparison with age-matched individuals. Conclusions Enlargement of long bone epiphyses with age appears to be a general tendency in the human skeleton. Our study shows that the enlargement of epiphyses may also be related to OA.

Background: The human homologue of the mouse progressive ankylosis (ANKH) gene is one of the key genetic factors involved in bone mineralization. Previous studies have shown that plasma levels of osteoprotegerin (OPG) and parathyroid hormone (PTH) are associated with the distal region of the ANKH gene, whereas skeletal size measurements are associated with the promoter region. Aim: The present study examines the possible phenotype–haplotype specificity of the associations in these two gene regions. Subjects and methods: The total sample consists of 1249 healthy individuals (mean age ¼ 47.7, SD ¼ 16.8) from 404 nuclear families. Fifteen interrelated anthropometric measurements were transformed into two principal components, reflecting body size and mass. Those, plus circulating levels of PTH and OPG, were subjected to association analysis, using transmission disequilibrium tests (TDTs) with ANKH gene. From 805 to 1150 individuals per SNP were genotyped. Results: In the proximal region (rs3006069–rs835154–rs835141), associations were found between the A–A–C haplotype and the first principal component reflecting body size (p � 0.048), whereas another haplotype, G–G–C, was associated with the first principal component, reflecting the body mass (p � 0.008). In the distal region of ANKH (rs39968–rs696294–rs875525), the A–A–C haplotype was found to be associated with OPG plasma levels (p � 0.001), whereas the G–A–C haplotype was associated with PTH circulating concentrations (p � 0.025). Conclusion: Taken together, the results show discrimination between the corresponding regions and haplotypes, suggesting trait-specific gene variants that influenced bone-related phenotypic variation in the studied population.

The substantial involvement of genetic factors in the determination of head-size and head-shape traits has been firmly established. However, there has been a lack of agreement on a number of specific issues concerning the pattern of inheritance of craniofacial features. In this study we examined some of these issues in a large, ethnically homogeneous sample of Indian pedigrees. The data included 1,263 individuals belonging to 373 nuclear families. Eleven raw head-size traits and two synthetic phenotypes, interpreted as horizontal and vertical head-size components (HOC and VEC, respectively), were used in the analysis. To establish the pattern of inheritance of head traits, we carried out univariate and bivariate analyses. Maximum heritability estimates ranged from 0.41 to 0.83 for the studied head-size phenotypes. The portion of the total residual variance attributable to putative additive genetic factors was 68.3% and 70.3% for HOC and VEC, respectively, and common familial factor effects were found to be nonsignificant. The extent of genetic influences did not differ significantly with respect to sex or between HOC and VEC. The results of bivariate variance decomposition analysis strongly suggest the existence of common genetic factors simultaneously affecting HOC and VEC; 41.8% of the two traits' total residual variance was attributable to the effect of these common genetic factors.

In the present cross-sectional study of the Chuvashian rural population, we examined the secular trends of age at menarche, the age at menopause, the reproductive period, and the age of the first marriage of Chuvashian women. The cohort included 745 women aged 18–90 years; age at menarche (N = 653) ranging from 10 to 24 years (mean 15.42 ± 2.11). Data regarding menopausal age was obtained from 316 women born between 1920 and 1950 (mean 48.5 ± 4.6). Statistical analyses included the maximum likelihood estimation and a Whiskers plot. Women born during the second through the fourth decade of the 20th century showed increasing mean values of age at menarche from 15.4 (second decade) up to 16.5 (fourth decade) and after that a decrease of the mean values to 14.0 (ninth decade). The mean values of menopausal age increased from 47.0 (women born from 1920 to 1925) to 49.3 (born from 1945 to 1950). Age at first marriage showed a trend of decreasing age. Our study demonstrated secular trends of age at menarche in Chuvashian women who had matured after World War II and also confirmed secular trends of increased age at menopause and the duration of the reproductive period. Women, whose maturation was during or immediately after World War II, showed a higher age at menarche and a higher dispersion of age at menopause.

Changes in the skeletal system, which include age-related bone and joint remodeling, can potentially be used as a biomarker of biological aging. The aim of the present study was to investigate the extent and mode of inheritance of skeletal biomarker of biological aging-osseographic score (OSS), in a large sample of ethnically homogeneous pedigrees. The investigated cohort comprised 359 Chuvashian families and included 787 men aged 18-89 years (mean 46.9) and 723 women aged 18-90 years (mean 48.5). The TOSS - transformed OSS standardized in 5-year age groups for each sex, was analyzed as a BA index. We evaluated familial correlations and performed segregation analysis. Results of our study suggest the familial aggregations of TOSS variation in the Chuvashian pedigrees. In a segregation analysis we found a significant major gene (MG) effect in the individual's TOSS with a dominant most parsimonious model (H(2) = 0.32). Genetic factors (MG genotypes) explained 47% of the residual OSS variance after age adjustment and after including sex-genotype interaction, they explained 52% of the residual variance. Results of our study also indicated that the inherited difference in the skeletal aging pattern in men lies mostly in the rate of aging, but in women in the age of the onset of the period of visible skeletal changes.

It is well known that regulation of calcium homeostasis in bone remodeling is one of the most crucial factors for maintaining healthy bones. Parathyroid hormone (PTH) is probably the most important hormone that participates in the bone remodeling process. Another important biochemical factor governing bone metabolism is osteocalcin (BGP). Although the physiological functions of both of these factors are well known, there is still very little known regarding their specific genetic determination and in particular, the specific genes that may regulate the circulating concentrations of these substances. In the present study, we examined whether nine single nucleotide polymorphisms (SNPs) in the human homologue of the mouse progressive ankylosis gene (ANKH)-one of the key genetic factors involved in bone mineralization-can be associated with PTH and BGP levels in apparently healthy human populations. The study sample comprised 244 nuclear families (840 individuals). After adjustment of BGP and PTH for the significant covariates (sex, age and BMI), the contribution of the putative genetic effects was statistically significant (P < 0.001) for both biochemical factors: 45.27 +/- 10.8% for PTH and 30.19 +/- 12.6% for BGP. Application of transmission disequilibrium tests (TDTs) revealed a significant association (P < 0.05) between PTH and two SNPs: rs39968 and rs875525. However, the association became particularly significant for four TDTs (P-values ranging from 0.0025 to 0.0008) when the association with the haplotypes generated from the above SNP was tested. This association remained significant even after correction for multiple testing with a false discovery rate of 0.05.

OBJECTIVE The objective of this study was to examine in an observational, cross-sectional, community-based study the secular trend of age at menopause among women in a rural Chuvashian population and to identify factors associated with age at menopause. DESIGN The sample included 316 postmenopausal women born between 1920 and 1950 with mean age at menopause of 48.47 +/- 4.63 (34-58) years. Statistical analyses included simple and multiple linear regression and "whiskers" plots. RESULTS Significant association was found between year of birth and age at menopause (beta = 0.194, P < 0.001) and reproduction period (P = 0.193, P < 0.001). Mean values of age at menopause increased from 47.0 years (born during 1920-1925) to maximal values of 49.7 years (born during 1940-1945) and 49.3 years (born during 1945-1950). Mean values of their reproductive period increased from 30.7 (born during 1920-1925) to maximal values of 34.1 (born during 1940-1945) and to 33.7 (born during 1945-1950). Multiple linear regression analysis demonstrated that year of birth was the only statistically significant (P = 0.19, P < 0.01) predictor of age at menopause. Age at menarche can also be a possible predictor of age at menopause (beta = -0.12, P = 0.04). CONCLUSIONS The study confirmed certain secular trends of age at menopause and reproductive periods in Chuvashian women. The authors also observed a negative association between age at menarche and age at menopause. The number of children and medical abortions as well as body mass index showed no association with age at menopause.

Osteoprotegerin inhibits osteoclastogenesis and plays an important role in the control of bone resorption. However, the genetic mechanisms underlying regulation of OPG levels are currently not fully elucidated. The aim of the present study was to determine whether the ANKH gene, which plays a central role in bone mineralization, contributes to the genetic regulation of OPG levels. A family-based association study used a sample of 159 ethnically homogeneous nuclear families, comprising 556 apparently healthy individuals. Statistical analyses included family aggregation analysis of OPG variation and four types of transmission disequilibrium tests. Each individual was genotyped for 11 SNPs in the ANKH gene. Four TDTs consistently showed a highly significant association between OPG levels and the intronic SNP rs875525 located between exons 6 and 7. The combined p-value for four tests to reject the null hypothesis of no association was 0.0003. Furthermore, haplotypes generated between rs875525 and two additional neighbouring SNPs (rs2291943 and rs2288474) also revealed a significant association with OPG plasma levels (p < 10(-4)-10(-3)). ANKH genetic polymorphisms in the area between SNP rs2291943 and rs2288474 are strongly associated with OPG plasma levels. The molecular mechanism underlying this association is not obvious, and therefore these results should be regarded cautiously until they are confirmed in independent studies.

Resume Objectifs L'arthrose est la plus frequente des arthropathies et serait un facteur de risque pour d'autres pathologies. Nous avons etudie le lien entre morbidite et arthrose radiographique des mains dans un echantillon de la population generale. Methodes Nous avons realise notre etude en Republique de Chuvashie (Federation de Russie), ou nous avons constitue une cohorte de 434 hommes âges de 18 a 86 ans et 385 femmes âgees de 18 a 84 ans. Le score de Kellgren et Lawrence a ete choisi pour rechercher la presence d'une arthrose. Les autres pathologies mentionnees dans les dossiers medicaux ont ete divisees en 14 categories par un medecin investigateur experimente. Pour etudier le lien entre morbidite et score radiographique d'arthrose de la main ajuste pour l'âge, nous avons fait appel a une analyse de la variance a un facteur, le score etant la variable dependante et la presence d'une pathologie donnee la variable independante (critere de classification). Resultats et conclusions Les scores d'arthrose etaient significativement plus eleves en cas de coronaropathie ischemique et significativement plus bas en cas de pathologie digestive. D'autres etudes devront s'efforcer de decouvrir le mecanisme biologique qui sous-tend le lien entre morbidite et arthrose.

Objectives Osteoarthritis is the most common form of joint disease and is considered to be a risk factor for other morbidities. We performed a population-based study to evaluate the association between morbidity and radiographic hand osteoarthritis. Methods Our population consisted of Chuvashians residing in peripheral villages of the Russian Federation. The investigated cohort included 434 males aged 18–86 years and 385 females aged 18–84 years. Osteoarthritis development was evaluated using the Kellgren and Lawrence grading scheme. Morbidity data was attained from their medical records and divided into 14 categories by an experienced research physician. To explore the relationship between morbidity and age-adjusted radiographic hand osteoarthritis score, one-way analysis of variance was used, with hand osteoarthritis score as a dependent variable and individuals affected vs. non-affected with the specific disease as an independent (grouping) variable. Results and Conclusions Statistically significant evidence linking radiographic hand osteoarthritis and morbidities was found in patients with ischemic heart disease and gastrointestinal diseases. Our research indicates that individuals with ischemic heart disease have higher values of radiographic hand osteoarthritis, compared to lower values in individuals with gastrointestinal diseases. Additional research is needed to understand the biological mechanisms of the association between morbidity and osteoarthritis.

The aim of this large, cross-sectional study was to describe the age- and sex-related variations of the somatotype, employing Heath and Carter's method, in a Chuvasha population residing in a rural region in central Russia. The investigated sample included 802 males aged 18-89 years (mean 46.9) and 738 females aged 18-90 years (mean 48.6). We evaluated the age and sex differences by one-way ANOVA with somatotype components as dependent variables and sex or age groups as grouping variables. Sex differences of somatotypes appear to be the strongest for endomorphy, with generally higher values in women. Endomorphy in males remained virtually unchanged after 30 years of age, but endomorphy in females kept increasing up to the 6th decade, and then subsequently decreased. Virtually no differences were noted in mesomorphy and a very small difference in ectomorphy between males and females aged 18-30 years. A reduction of sexual dimorphism in all somatotype components after age 70 was also observed. The largest difference of all somatotype components appeared between age groups 18-30 and 31-40 years. Thereafter, somatotypes remained practically unchanged. Mesomorphy continued to increase until the 5th decade in both sexes, while in females, endomorphy continuously increased until their 6th decade. In the 7th and 8th decades, a decrease in mean values was observed. Mesomorphy and ectomorphy showed opposite age-related trends. Results of our study clearly suggest that in physique investigations, the somatotypes need to be studied in each sex separately, and in studies of young people, they need also to be adjusted to age.

Summary Background Measurement of angiogenin in plasma provides important prognostic and diagnostic information in variety of malignancies and may even correlate with cancer's progression. Nevertheless, nowadays, specific physiological mechanisms of this protein action as well as major factors regulating its circulating levels normally and in pathology are still poorly understood. The main objectives of this study were to examine the contribution of a number of endogenous factors, such as sex, age, body size and genetic effects on the production of angiogenin in apparently healthy individuals, and to assess the correlations in circulating levels between angiogenin and other molecules involved in angiogenesis. Methods The plasma levels of angiogenin and each of the additional cytokines [interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), macrophage-colony stimulating factor (M-CSF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), soluble intercellular adhesion molecule-1 (sICAM)] were determined by enzyme-linked immunoassay in a large family based sample. Results Angiogenin levels were significantly higher in man than in women (360·64 104·04 ng/ml vs. 322·15 100·34 ng/ml, P

Introduction Bone size is an important determinant of bone strength. Although it is well established that bone size traits are under the strong genetic control, genes involved in their determination are poorly characterized. The major objective of the present study was to test hypothesis of possible association between three RUNX2 SNP polymorphisms (rs2819858, rs1406846, rs2819854) and anthropometrical femoral length (FEML). In addition, the possibility of association between anthropometrical tibial length (TIBL) and stature and chosen RUNX2 polymorphisms was tested. Materials and methods The study was conducted on 265 nuclear families comprised of a total of 904 individuals. DNA samples were available for 705 individuals, belonging to 212 nuclear families. Three different transmission disequilibrium tests (TDTs), population-based and pedigree-based (PDT) association analyses were implemented in order to test the working hypothesis. Results The results unambiguously and consistently demonstrated significant association for FEML regardless of the specific polymorphism tested and type of analysis implemented. The P values obtained by TDTs ranged between 0.0155 and 0.0007. The effect of RUNX2 polymorphisms was estimated to explain 1.9% of the total FEML variation after adjustment for sex and age. The data suggested that the strength of association between RUNX2 polymorphisms and FEML may be higher in females ( P = 0.007) than in males ( P = 0.046), according to PDT. Conversely, no reliable evidence of association between RUNX2 polymorphisms and either TIBL or stature was found. Conclusions For the first time, the evidence of association between RUNX2 polymorphisms and FEML was provided. The results of the present research contribute to the deeper understanding of the genetic architecture of femoral size and introduce the issues of site and sex dependency of the extent of RUNX2 effect. Further studies are required to confirm our findings, specifically focused on clinically oriented sites of skeleton, like femoral neck.

Resume Objectifs. – Evaluer de maniere quantitative la contribution relative des signes radiographiques degeneratifs caracteristiques de l'arthrose, comme l'osteophytose, le pincement de l'interligne articulaire, la condensation osseuse sous-chondrale, les geodes sous-chondrales, la deformation laterale et la dislocation corticale, dans l'etablissement du score de la classification radiographique de Kellgren et Lawrence (K-L) pour l'arthrose de la main. Methodes. – Des radiographies des deux mains ont ete effectuees chez les 1245 sujets d'origine Tchouvache (Federation de Russie) qui ont ete inclus dans cette etude. Sur chacune des quinze articulations de chaque main ont ete evalues d'une part le score de K-L et d'autre part les six signes radiographiques precites de l'arthrose. Des analyses de regression multiple et de correlation ont ete effectuees pour chaque rangee d'articulations des doigts et pour les groupes articulaires du pouce, ainsi que pour ces groupes articulaires repartis en six tranches d'âge. Resultats et conclusion. – Selon la methodologie de la classification de K-L, la participation relative de l'osteophytose a ete grande a toutes les etapes de l'analyse. Le pincement de l'interligne articulaire et la condensation osseuse sous-chondrale avaient joue un role important dans la determination du score de K-L chez les sujets âges de moins de 40 ans, mais un role moindre chez ceux plus âges. A l'inverse, l'impact des geodes sous-chondrales et de la deformation laterale a ete insignifiant a la phase de debut de l'arthrose (c'est-a-dire chez les sujets jeunes), mais important dans la determination du score de K-L chez les sujets plus âges. La dislocation corticale n'a pas eu d'influence sur le score de K-L.

Our objective was to clarify how different groups of chronic morbidities are associated with indices of body composition, such as body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR), skinfold index (SF), and fat-free mass index (FFMI). Our sample comprised Chuvasha residing in numerous villages in a rural area of the Russian Federation. The investigated cohort included 787 males aged 18-89 years, and 716 females aged 18-90 years. We performed a cross-sectional, community-based study of a large sample of individuals not receiving any medications for treatment or prevention of chronic morbidities. To elucidate the association between morbidity and age-adjusted anthropometrical indices, we used one-way analysis of variance, wherein the above indices were the dependent variables, while individuals affected vs. nonaffected for a specific disease were the grouping variables. Individuals with ischemic heart disease, diabetes mellitus, hypertension, and peptic ulcer showed significant differences in their BMI, WC, WHR, and SF. In the first diseases, mean values of anthropometric indices were higher in affected individuals, whereas in the peptic ulcer group, mean values were higher in the nonaffected. Skin diseases and gynecological diseases showed significant differences in WHR. Mean values in affected individuals were lower than in the nonaffected. The group afflicted with local forms of arthritis showed significant differences in FFMI, suggesting that arthritis is not linked to obesity, but is linked to high lean mass. Rheumatic diseases positively correlated with WC and FFMI.

Osseographic score (OSS) is a skeletal biomarker of biological aging, based on assessment of the hand's radiographic features. The aims of the present cross-sectional and follow-up study were: 1) to evaluate age-related changes of OSS in a large Chuvashian cohort, and 2) to evaluate sex differences in age-related changes of OSS. This study reports on intersexual differences in the pattern of skeletal aging. The most prominent difference was in the rate of skeletal change, measured as average OSS difference per year. However, no differences were found in the age at which the first skeletal change occurred. The mean values of OSS were higher in males than in females in decades 3-5 of life, but afterwards they reversed. In a follow-up study, we found that sex differences regarding the rate of OSS change began in the fifth decade, but became statistically significant only in the sixth and seventh decades. Thereafter, the rate of OSS change again became virtually equal between sexes.

Objectives. – to assess quantitatively the relative contribution of joint degeneration characteristics such as osteophytes (OS), joint space narrowing (JS), subchondral sclerosis (SS), subchondral cysts (SC), lateral deformity (LD) and cortical collapse (CC) to the Kellgren and Lawrence (K–L) score grade of hand osteoarthritis (OA). Methods. – Radiographs of both hands were taken from 1245 study participants, native Chuvasha, Russian Federation. K–L score and the six above-mentioned characteristics were assessed on 15 joints of each hand. Multiple regression and correlation analyses were performed: for rows of hand joints and groups of thumb joints, and for the aforementioned rows but assigned into six age groups. Results and Conclusions. – According to the K–L grading system the relative contribution of OS to joint degeneration was high in all stages of the process. JS and SS played an important role in determining the K–L score in persons younger than 40 but less so in older people. Conversely, influence of SC and LD is insignificant at the onset of OA (i.e., in young persons), yet in older people it was a leading determinant of the K–L score. CC exerts no influence on the K–L score of OA.