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Biomedical subjects

G Livshits

Publications and source records attributed to G Livshits.

At least 19 recordsLinked to original sources
PubMed2007

Genetic and environmental determinants of circulating resistin level in a community-based sample.

OBJECTIVE: Resistin is a hormone secreted by adipose tissue, monocytes, bone marrow, and other tissues. It was also proclaimed as an important link between obesity and diabetes. The main objective of this study was to elucidate the contribution of a number of endogenous factors, such as sex, age, obesity characteristics, and genetic effects to the production of resistin in apparently healthy individuals. We also tested the possible relationships between circulating levels of resistin and other adipokines (leptin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)). MEASUREMENTS: The plasma levels of studied adipokines were determined by enzyme-linked immunoassay in pedigree-based sample (n = 616), and subjected to model-based quantitative genetic analysis. RESULTS: Resistin levels were significantly higher in women than in men (3.60 +/- 2.53 vs 3.15 +/- 2.48 ng/ml, P < 0.001), and varied independently of age in either sex. Statistical-genetic analysis revealed significant familial correlations (P < 0.01) for resistin. Adjusted for covariates, 66.38 +/- 10.28% of the resistin variation was attributable to putative genetic factors. A relatively small portion of the resistin variation (11.54 +/- 5.77%) was attributable to sharing a common household environment. The remaining variation, 22.12 +/- 17.69% was due to random environmental (i.e., unmeasured non-additive genetic) effects. The results of our analysis showed modest significant correlation of resistin with TNF-alpha and IL-6, and only in some groups; thus, while resistin was correlated with TNF-alpha in men, the correlation with IL-6 was significant only in the post-menopausal women group. CONCLUSIONS: Our observations indicate that resistin is strongly influenced by genetic factors. The high heritability estimates for resistin concentrations clearly suggest the continuing need for further molecular genetic investigations.

Adolescent↗
PubMed2006

Osteoprotegerin plasma levels are strongly associated with polymorphisms in human homologue of the mouse progressive ankylosis (ANKH) gene.

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.

Adult↗
PubMed2005

Contribution of the familial and genetic factors on monocyte chemoattractant protein-1 variation in healthy human pedigrees.

Monocyte chemoattractant protein-1 (MCP-1) is a chemokine whose circulating levels have been detected in the lesions of several diseases such as pulmonary fibrosis, rheumatoid arthritis and atherosclerosis. However, the factors involved in the regulation of its production remain largely unknown. The main aim of the present paper was to ascertain the contribution of the familial/genetic factors on the production of MCP-1 in apparently healthy individuals. We also tested the possible relationships between the plasma levels of MCP-1 and other cytokines involved in bone metabolism (receptor activator NF-kB ligand (RANKL), osteoprotegerin (OPG), interleukin-6, macrophage-colony stimulating factor, tumor necrosis factor-alpha). Using ELISA assays the cytokine levels were measured in 570 apparently healthy individuals belonging to ethnically homogeneous Caucasian families. We found that MCP-1 levels were significantly (P<0.01) correlated with RANKL (in both sexes) and with OPG only in women. The study showed that adjusted for potential covariates, 72% of the MCP-1 variance, was attributable to familial effects. About 49% was due to potential genetic factors and the rest was explained by common environmental sources shared by spouses within each family. In conclusion, our data provide reliable evidence for the substantial role of genetic factors in the determination of the phenotypic variability of MCP-1 plasma levels. The association between the osteoclastogenic cytokines and MCP-1 levels in healthy pedigrees is of special interest and might shed light on MCP-1 involvement in bone remodeling.

Adult↗
PubMed2005

Association of leptin levels with obesity and blood pressure: possible common genetic variation.

OBJECTIVE: To ascertain the extent to which relationships between obesity (OB) and blood pressure (BP) can be explained by an individual's leptin plasma levels. DESIGN: Pedigree-based cross-sectional study in an apparently healthy population of European origin. SUBJECTS: The study sample is comprised of 90 nuclear and more complex families totaling 210 male and 213 female subjects aged 18-75 y, randomly recruited in Bashkorstan Autonomic region, Russia. MEASUREMENTS: Various fatness and fat distribution traits (including nine circumferences (CRCs), and eight skinfolds (CKFs) by anthropometry), blood pressure, and plasma leptin levels (by ELISA kits). RESULTS: Adjustment for circulating leptin led to attenuation of the magnitude of correlations between OB and BP, regardless of trait pair and sex cohort. Some of these correlations became statistically nonsignificant. All familial effects were gone, and heritability estimates became virtually zero after adjustment of each of the OB traits and systolic blood pressure (SBP) in offspring for leptin values in parents. CONCLUSION: BP and OB covariation is substantially mediated by circulating leptin levels. As a result, body fat has only a weak independent effect on BP variation after adjustment for leptin levels. Our findings also strongly suggest that genetic variation in body mass index, SKFs, and even body CRCs, as well as of SBP is due to genetic variation of leptin. Genetic variation of diastolic blood pressure in the present sample, however, shared very little with that of leptin.

Adolescent↗
PubMed2005

Applications of pooled DNA samples to the assessment of population affinities: short tandem repeats.

Pooled DNA samples have been used in association studies of Mendelian disease genes. This method involves combining equal quantities of DNA from patients and control subjects into separate pools and comparing the pools for distributions of genetic markers. In this study identical quantities of DNA from 300 individuals representing 6 populations were pooled and amplified for 296 loci using the touchdown polymerase chain reaction (PCR) method. The purpose of this study is to test the efficacy of pooled DNA markers in the reconstruction of the genetic structure of human populations. The populations sampled included Chuvash, Buryats, Kizhi, Native Americans, South Africans, and New York City whites. To test the accuracy of the allele-frequency distributions, we genotyped the Buryats and New York samples individually for six microsatellite markers and compared their frequencies to the allele frequencies derived from the electropherogram peak heights for the pooled DNA, producing a correlation of 0.9811 with a variance of less than 0.04. Two-dimensional scaling of genetic distances among the six populations produced clusters that reflected known historical relationships. A distance matrix was created using all 296 loci, and matrices based on individual chromosomes were correlated against the total matrix. As expected, the largest chromosomes had the highest correlations with the total matrix, whereas one of the smallest chromosomes, chromosome 22, had the lowest correlation and differed most from the combined STR distance matrix.

Alleles↗
PubMed2004

Heritability of circulating growth factors involved in the angiogenesis in healthy human population.

The present study examined the extent of genetic and environmental influences on the populational variation of circulating growth factors (VEGF, EGF) involved in angiogenesis in healthy and ethnically homogeneous Caucasian families. The plasma levels of each of the studied biochemical indices were determined by enzyme-linked immunoassay in 478 healthy individuals aged 18-75 years. Quantitative genetic analysis showed that the VEGF and EGF variation was appreciably attributable to genetic effects, with heritability estimates of 79.9% and 48.4%, respectively. Yet, common environmental factors, shared by members of the same household, also played a significant role (P < 0.01) and explained between 20.1% and 32.6% of the variation. The present study additionally examined the covariations between these molecules and either transforming growth factor-beta 1 (TGF-beta 1) or tissue inhibitors of matrix metalloproteinases 1 (TIMP-1), likewise relevant for angiogenesis. Bivariate analysis revealed significant phenotypic correlations (P < 0.002) between all pairs of variables, thus indicating the possible existence of common genetic and environmental factors. The analysis suggested that the pleiotropic genetic effects were consistently the primary (or even the sole) source of correlation between all pairs of studied molecules. The results of our study affirm the existence of specific and common genetic pathways that commonly determine the greater part of the circulating variation of these molecules.

Adult↗
PubMed2003

The contribution of familial resemblance to variation in circulatory levels of tissue inhibitors of metalloproteinases and transforming growth factor-beta1.

This study attempted to elucidate the genetic and environmental factors influencing interindividual variation of circulating TIMP-1, TIMP-2 and TGF-beta1 and to clarify the relationship between the latter biochemical indices and hand osteoarthritis in an ethnically homogeneous sample. Plasma levels of each of the above biochemical indices were measured in 401 healthy individuals (aged 18-75 years) belonging to 90 nuclear and more complex families. Variance component analysis showed that a major part of the interindividual differences in TGF-beta1, TIMP-1 and TIMP-2 levels was credibly attributable to genetic and familial factors. Adjusted for significant covariates, the putative genetic effects on the above three amounted to 0.40 +/- 0.10, 0.47 +/- 0.11 and 0.72 +/- 0.10, respectively. Common environmental factors, shared by members of the same household, also contributed significantly ( P < 0.01) to variation of each of the biochemical indices and explained between 27.6% (TIMP-2) and 38.7% (TGF-beta1) of their variation. A bivariate analysis revealed a strong and highly significant correlation between TIMP-1 and TGF-beta1 (r = 0.58, P < 0.001), which was due to common genetic and environmental sources (r(G) = 0.62 +/- 0.09, r(E) = 0.31 +/- 0.11, both P < 0.001). The analysis also detected modest but significant genetic correlation between TIMP-1 and TIMP-2 (r(G) = -0.307 +/- 0.108, P < 0.01). The present study evinces a strong genetic dependence for the plasma levels of both TIMPs and TGF-beta1 and provides a basis for the further analysis of genetic variation affecting and regulating the circulatory concentrations of TIMPs and TGF-beta1 in healthy humans.

Adolescent↗
PubMed2003

Association and linkage disequilibrium analyses suggest genetic effects of estrogen receptor alpha and collagen IA1 genes on bone mineral density in Caucasian women.

Estrogen receptor alpha (ER alpha) and collagen IA1 (COLIA1) genes have been suggested as possibly implicated in reduced bone mineral density (BMD). The present study investigated the occurrence of association and linkage disequilibrium between radiographic hand BMD and polymorphic alleles of ER alpha and COLIA1 genes, in human pedigrees of a Chuvasha population in Russia. The study sample included 463 members of 113 pedigrees, mostly nuclear families. We performed association and transmission disequilibrium test (TDT) analyses of the combined PvuII and XbaI RFLPs alleles on the same chromosome (haplotype) of the ER alpha gene with BMD Z scores of cancellous or cortical bone in the hand phalanges. The association analyses were performed separately for both genders in the parental generation, i.e., 'fathers' (n = 114; average age 64.2 y) and 'mothers' (n = 122; average age 62.7 y). The Px haplotype was associated significantly with lower BMD Z scores in 'mothers' only. The difference between subjects who carried one or two copies of the Px haplotype and those lacking it was 0.68 Z scores, P = 0.003 and 0.51 Z scores, P = 0.025 for cancellous and cortical bone, respectively. Multiple linear regression model with age, height, weight, and Px haplotype status as predictors explained 26.7% and 28.3% of the total observed variance in BMD with Px haplotype as independent predictor explaining 5.9%; P = 0.002 and 3%; P = 0.028 (cancellous and cortical bone, respectively). Results of t-TDT for triads of two parents and just one of their female offspring (but not male offspring) suggested the existence of linkage disequilibrium between the two loci of Px haplotype and BMD trait (P = 0.047). No association was found between polymorphic alleles of COLIA1 gene and BMD, but 'mothers' with combined genotypes of Px haplotype of ER alpha gene and "s" allele of COLIA1 gene had the lowest mean Z scores (-0.944 and -0.788 for cancellous and cortical bone, respectively). We conclude that the Px haplotype of the ER alpha gene is associated with low BMD values in females, as the phenotype is gender dependent (the association was not observed in males), and the "s" allele of COLIA1 gene in combination with this haplotype contributes to reduced BMD.

Adolescent↗
PubMed2003

Genetic effects of estrogen receptor alpha and collagen IA1 genes on the relationships of parathyroid hormone and 25 hydroxyvitamin D with bone mineral density in Caucasian women.

There is a growing body of evidence that estrogen receptor alpha (ERalpha) and collagen IA1 (COLIA1) genes may affect bone mineral density (BMD) levels in postmenopausal women. In a recent study we found that the Px haplotype of the ERalpha gene (resulting from combined PvuII and XbaI restriction fragment-length polymorphisms [RFLPs] in intron 1) was associated with low radiographic phalangeal hand BMD in elderly women (62.7 +/- 6.5 years of age), of European origin. The combination of the Px haplotype and "s" allele of the COLIA1 gene (MscI RFLP in Sp1 locus) decreased BMD in these women. The major aim of the present study was to investigate whether the genetic effects of these genotypes on cancellous and cortical hand BMD, in the same elderly women (N = 122), are possibly mediated through circulating levels of parathyroid hormone (PTH) and/or 25 hydroxyvitamin D [25(OH)D], and may be related to biochemical markers of bone turnover (propeptide of type I procollagen [PICP] and osteocalcin). Multiple regression analyses of age-adjusted cancellous BMD revealed that ERalpha polymorphism and circulating levels of PTH were independent predictors of about 12.9% of its variation. Some 17.9% of cortical BMD variations were attributable to the combined effects of ERalpha polymorphism and plasma concentrations of 25(OH)D, estradiol, and PTH. The significant inverse association between PTH and BMD of both types was further confirmed by association analysis according to categorical subgroups of BMD values, as well by haplotype status. The mean difference in PTH concentrations between subjects carrying the Px haplotype (higher mean) and those lacking it (lower mean) reached 0.59 SD (P =.01). The difference in PTH levels further increased when explored in the 4 subgroups formed by combinations of polymorphic ERalpha and COLIA1 genotypes. Mean PTH of subjects carrying both the Px haplotype and "s" allele was higher by 1.52 SD (P =.001) than in subjects lacking both the Px haplotype and "s" allele. Those carrying both Px haplotype and "s" allele were also characterized by highest mean value of PICP and lowest means of 25(OH)D and BMD (both tissue types). We conclude that in the studied elderly women, the Px haplotype may be involved in causing the phenotypic expression of higher circulating levels of PTH and higher bone turnover, which, in turn, may lead to bone loss.

Aged↗
PubMed2003

Search for linkage between hand osteoarthritis and 11q 12-13 chromosomal segment.

OBJECTIVE: The aims of the present study were: (1) to evaluate the extent and mode of inheritance of hand osteoarthritis by using a large sample of ethnically homogeneous pedigrees of Caucasian origin; (2) to examine whether the synthetic measure of osteoarthritis according to Kellgren and Lawrence (K-L) and the more specific measure, namely, the extent of osteophytes development, have a similar putative genetic determination and pattern of biological inheritance and (3) to test the hypothesis that hand osteoarthritis dependent phenotypes are linked to the 11q 12-13 chromosomal region. METHODS: The population of the present study comprised 1190 Chuvashians (Russian Federation) belonging to 295 nuclear families. Segregation analysis was carried out on a total sample. Sub-sample of 571 individuals was used to conduct Transmission/disequilibrium test (TDT) and model-based linkage analysis. RESULTS: Adjusted for age, sex and other covariates, both OA phenotypes showed significant familial aggregation. The model fitting analysis strongly supported the hypothesis of a major gene effect on study traits. The inferred major gene explained about 52% of the osteophyte score (OPS) and 49% of the K-L score variation adjusted for confounding variables. The series of model-based linkage analyses and TDTs provided inconclusive evidence on possible linkage of both phenotypes to the 11q 12-13 chromosomal region. CONCLUSIONS: We support the hypothesis of a major gene effect in heritability of hand osteoarthritis in both phenotypes. Despite the fact that some DNA markers showed statistically significant association to studied primary phenotypes, we find only weak evidence of linkage disequilibrium between hand osteoarthritis and the proximal part of the 11q 12-13 chromosomal segment (D11S1983 for K-L score and D11S1313 for OPS). The subject, however, a merit requires further investigation.

Adolescent↗
PubMed2003

Quantitative genetic study of radiographic hand bone size and geometry.

Despite the obvious epidemiological significance of bone size (BS) and geometry (BG) traits as risk factors for osteoporotic fracture, very little is still known concerning the extent of their genetic determination. In the present paper we report the results of quantitative genetic analysis of a number of BG and BS indices, as well as of BMD measurements, obtained on a large pedigree-based sample (296 nuclear families, 1208 individuals) of plain hand radiographs. The families studied were all ethnically Caucasians (Chuvasha) living in small villages along the Volga River (Russia). The sample consisted of 636 men and 572 women, aged 18-91 years. To assess hand bone size we used the outcome of principal component analysis conducted on 48 measurements of metacarpal bones and proximal phalanges (PC-BS). Two BG indices, average metacarpal cortical index and breaking bending resistance index (BBRI), also measured on metacarpal and proximal phalanges were used. Again the outcome of the principal component PC-BBRI was examined in the genetic analysis. PC-BS measurements strongly correlated with body length (r = 0.75, P < 0.001) and weight (r = 0.39, P < 0.001), suggesting that they indeed reflected hand skeleton size. Familial correlations for all studied traits, adjusted for covariates (sex, age, etc.), were all highly significant statistically. For example, parent/offspring correlations ranged between 0.248 (P < 0.001) for phalangeal BMD and 0.385 (P < 0.001) for PC-BBRI. Maximum likelihood estimates of the variance component analysis confirmed these results, indicating that approximately 58 to 66% of the residual variance of the studied traits was attributable to genetic effects. Bivariate analysis clearly revealed that while genetic variation of the phalangeal BMD was independent of the genetic effects influencing hand BS and BG, the latter two were strongly interrelated. A substantial proportion of PC-BS and PC-BBRI variation was due to shared genetic (r(G) = 0.468 +/- 0.063) and environmental (r(E) = 0.704 +/- 0.052) factors.

Adolescent↗
PubMed2002

Transmission disequilibrium test for hand bone mineral density and 11q12-13 chromosomal segment.

The main aim of the present study was to test the hypothesis that the bone mineral density (BMD) assessed from radiographs of the hand phalanges in a random sample of ethnically homogeneous pedigrees is linked to the 11q12-13 chromosomal segment. The data for the study were gathered from 574 Chuvasha individuals belonging to two- and three-generation pedigrees who live in small villages in the Bashkortostan autonomy, Russia. Preliminary statistical-genetic analysis of the BMD in the pedigrees studied showed that potential genetic effects were highly significant ( p<0.001, in comparison with the model assuming no genetic effect), and explained at least 36% of the BMD variation adjusted for sex and age differences. For the transmission/disequilibrium test (TDT) used in our study, a total of 163 nuclear families with two sibs on average were available. Seven DNA microsatellite markers ( D11S1313, D11S1765, D11S987, D11S913, D11S983, D11S1314, D11S916) with average spacing of 2 cM on the chromosomal area 11q12-13 were selected for the TDT. The nominal p values ( p<0.05-0.0015) obtained from three TDT-type tests used for random and extreme-threshold sampling designs pointed consistently to possible linkage disequilibrium between BMD and some of the DNA markers. There was evidence for possible linkage disequilibrium in the upper part of the chromosomal segment studied (markers D11S1313 and D11S1765), and also in the lower part (markers D11S1983 and D11S1314). The lowest nominal p values (0.0015-0.0067) were obtained from three TDT-type tests for marker D11S1313. However, our findings must still be treated with great caution.

Adult↗
PubMed2002

Evidence for a major gene for bone mineral density/content in human pedigrees identified via probands with extreme bone mineral density.

Bone mineral content (BMC) and/or bone mineral density (BMD, i.e. BMC scaled by bone size) are major determinants for osteoporosis, which is a serious health problem. The major determinant of variation in BMD/BMC is genetic. The few studies now available are inconsistent in the identification and/or even in the existence of major gene(s) for BMD/BMC. In 51 human pedigrees with 941 individuals (526 measured for phenotypes) identified via probands with extreme BMD values, we performed complex segregation analyses to test the existence of a genetic locus with a major effect on BMD/BMC variation. We analyzed BMD and BMC at the spine, hip and wrist jointly by employing, as the study phenotype, factor scores (FS) of the principle component that explains approximately 75% of the total BMD/BMC variation at the three sites. The results indicate that a major gene exists with a codominant effect that is responsible for approximately 16% of the FS variation when adjusted for significant effects of sex, body weight and age. A significant genotype-x-sex-x-age interaction was found, which may explain approximately 14% of the FS variation after adjusting for body weight. Testing of various models did not provide support for shared familial environmental effects but suggested the existence of residual polygenic effects, which may explain approximately 50% of the FS variation when adjusting for sex, body weight and age. This study indicates a promising aspect of studies to identify a major gene for BMD/BMC variation in our pedigrees identified via extreme probands.

Bone Density↗
PubMed2002

Relationship between parameters of early growth in Israeli infants.

A sample of 1931 Israeli infants was measured for body weight (WT), length (HT) and head circumference (HC) for approximately 2 years. The Count model with 3 parameters was chosen as the best fitting and most parsimonious function to approximate growth of all 3 studied traits. In the model parameter a relates to birth indices, b--to velocity of growth, and c--to rapid early childhood growth, or acceleration. Assuming a difference in growth patterns in the periods of different length, the whole sample was divided into 3 groups: 1) infants with last measurement around the age of 12 months; 2) infants with last measurement around the age of 18 months, and 3) infants with last measurement around the age of 24 months. The individuals measured up to 12 months were presented in all three groups. 27 curve fitting parameters, corresponding to 3 different follow-up intervals for WT, HT and HC were computed for each individual. A high correlation was detected between the a parameters regardless of time interval for 3 measured traits. A negative correlation was found between b and c parameters within the same time interval. A consistent positive correlation was indicated between a and b parameters, especially for body length and head circumference. A principal component analysis extracted five independent factors explaining 88.1% of the total variance. Three first factors retained parameters b and c, describing growth rate and pattern of each trait separately, namely, F1 was responsible for head circumference, F2 was a body length factor, F3 was a body weight factor. F4 extracted all birth indices, observed (HC0, HT0 and WT0) and expected (parameters a). The composition of principal factors allowed us to assume that there might be a strong involvement of a pleiotropic genetic source in determination of birth size traits and an independent genetic source controlling the pattern of growth for each trait separately.

Anthropometry↗
PubMed2001

Familial history, age and smoking are important risk factors for disc degeneration disease in Arabic pedigrees.

The present study used computed tomography imaging to evaluate the extent and pattern of the intergenerational transmission of spinal disc degeneration disease (DDD) in complex pedigrees. Contribution of a number of the potential covariates was also studied using univariate and multivariate logistic regression analysis, as well as two types of complex segregation analysis models. Among 161 individuals studied, DDD was diagnosed in 60 individuals. The number of protruded discs varied from 1 to 4, mostly in lumbar or lumbosacral regions. The average age at onset of the disease was similar for both women (36.0 years) and men (34.8 years). The proportion of the individuals affected by the DDD status of their parents ranged from 10% in families of two healthy parents to 55.5% of two affected parents (p < 0.01). The results of the logistic regression analyses and complex segregation analysis were qualitatively the same: DDD status of parents, age and smoking were the main risk factors for disc herniation in the Arabic families we examined. All analyses showed a predominating role of the family history as a risk factor for DDD in offsprings. It showed, for example, four times higher risk at age 50 for individuals with two affected parents vs. those who have two non-affected parents. However, the results of models-fitting genetic analysis, did not confirm a monogenic Mendelian pattern of inheritance.

Adult↗
PubMed2001

Familial factors of blood pressure and adiposity covariation.

In the present study, we used the maximum likelihood approach as implemented by variance analysis and attempted to quantify genetic and environmental components of variance in systolic (SBP) and diastolic (DBP) blood pressure in 514 individuals who belonged to a total of 135 nuclear families of Chuvasha, Russia, ethnic origin. The extent to which these interindividual differences depend on age, gender, body mass index (BMI) and other anthropometric measurements was investigated. Major findings include the following. (1) The variation in both SBP and DBP was significantly affected by genetic factors (h(2)(SBP)=0.51+/-0.13, h(2)(DBP)=0.20+/-0.09), shared household environment, and age. These effects were stronger with respect to SBP, which also showed significant gender differences in baseline values and rate of SBP increase with age. (2) Genetic and common household factors, as well as undetected residual effects, were not completely independent. The respective 3 facets of correlation between SBP and DBP were significant: 0.66+/-0.10, 0.76+/-0.11, and 0.55+/-0.14. (3) SBP and DBP each showed significant phenotypic correlations with BMI and anthropometric factors. These correlations had a substantial genetic component but were not equal for SBP and DBP. SBP showed the highest genetic correlation with arm circumference (r(G)=0.63), whereas for DBP, this was found with hip skinfold (r(G=)0.88). (4) Bivariate heritability estimates, as well as adjustment of BP measurements for BMI and selected anthropometrics, indicated that DBP likely does not have independent genetic heritability. The residual genetic variance of adjusted SBP remained significant, although substantially lower in comparison with the nonadjusted h(2).

Adipose Tissue↗
PubMed2001

Bone mineral density is associated with estrogen receptor gene polymorphism in men.

In order to identify genetic effects of allelic variation on bone mineral density (BMD), association studies have been performed recently. Examining the relation between PvuII and XbaI restriction fragment length polymorphism (RFLPs) at the estrogen receptor (ER alpha) gene and BMD, in women or men, have yielded conflicting results. We analyzed the association between this polymorphism and BMD Z score values of cancellous bone at the 3rd finger in 344 members of nuclear families of European population, Chuvasha, living in Russia. The population sample included 183 males, aged 18-84, and 161 females, aged 23-79. The analysis has been performed separately for both sexes and for both generations (parents and offspring). We used a novel direct haplotyping method, which determines simultaneously each of the PvuII and XbaI RFLPs and their relation to each other. The haplotypes were represented as the combination of both polymorphic sites on the same chromosome, by using P/p and X/x for PvuII and XbaI restriction sites, respectively. The subjects were classified into 3 groups of genotypes: A = PXPX (homozygote for the PX haplotype); B = PXPx, PXpx (the heterozygotes for the PX haplotype); C = PxPx, Pxpx, pxpx (genotypes that are lacking the PX haplotype). The PXPX genotype (A) was associated with higher BMD Z score values in comparison to the genotypes that are lacking the PX haplotype (C), in total males [0.618 vs. -0.133 (p = 0.004)] and for the "sons" generation [0.724 vs. -0.198 (p = 0.02)]. Similar tendency was observed for the "fathers" generation (0.539 vs. -0.085), though the difference did not approach statistical significance (p = 0.087). These findings were not found in the female samples, nor in the "mothers" or "daughters" generations. The question if there are differences in the mode of action of estrogen through its receptor on bone mass, between the genders or between the males' generations, have to be further investigated.

Adolescent↗