Recent progress in understanding the genetic susceptibility to osteoporosis

Zmuda, Joseph M.; Cauley, Jane A.; Ferrell, Robert E.

doi:10.1002/(sici)1098-2272(1999)16:4<356::aid-gepi3>3.0.co;2-i

Cited by 83 publications

(40 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in adjusted analysis of patella lead concentrations, there was evidence of effect modification by APOE genotype on relations of gender with patella lead concentrations. The APOE ε4 allele is associated with lower bone mineral density and higher bone turnover rates 40,55 ; our findings may suggest that among men, the allele was associated with lead loss that exceeded bone mineral loss, but among women, the allele was associated with bone mineral loss that exceeded lead loss, as might be expected.…”

Section: Differences By Agementioning

confidence: 87%

“…34,35 Because of a growing literature that suggests the toxicokinetics of lead may be modified by genetic polymorphisms, 36,37 we also evaluated associations with 2 genes thought relevant to deposition or release of lead or calcium from bone: apolipoprotein E, APOE, and vitamin D receptor, VDR (by using 2 restriction enzymes, Bsm I and Fok I). [38][39][40][41] Genotyping was performed in the laboratory of the Malaria Institute in the Bloomberg School of Public Health by standard methods.…”

Section: Laboratory Methodsmentioning

confidence: 96%

See 1 more Smart Citation

Gender and Race/Ethnicity Differences in Lead Dose Biomarkers

et al. 2008

View full text Add to dashboard Cite

Objectives. We sought to identify predictors of lead concentrations in the blood, tibias, and patellae of older adults and to describe differences by gender, race/ ethnicity, and other factors that can influence lead toxicokinetics and, thus modify health effects.Methods. Participants aged 50 to 70 years (N = 1140) were randomly identified from selected neighborhoods in Baltimore, Maryland. We measured lead concentrations by anodic stripping voltammetry (in blood) and 109 Cd-induced K-shell x-ray fluorescence (in bone). We used multiple linear regression to identify predictors of lead concentrations.Results. Mean (SD) lead concentrations in blood, tibias, and patellae were 3.5 (2.4) µg/dL, 18.9 (12.5) µg/g, and 6.8 (18.1) µg/g, respectively. Tibia concentrations were 29% higher in African Americans than in Whites (P < .01). We observed effect modification by race/ethnicity on the association of gender and physical activity to blood lead concentrations and by gender on the association of age to tibia lead concentrations. Patella lead concentrations differed by gender; apolipoprotein E genotype modified this relation.Conclusions. African Americans evidenced a prominent disparity in lifetime lead dose. Women may be at higher risk of release of lead from bone and consequent health effects because of increased bone demineralization with aging.

show abstract

Section: Differences By Agementioning

confidence: 87%

Section: Laboratory Methodsmentioning

confidence: 96%

Gender and Race/Ethnicity Differences in Lead Dose Biomarkers

et al. 2008

View full text Add to dashboard Cite

show abstract

“…25 However, BMD is not the only determinant of skeletal fragility. Bone size and geometry also determine bone mechanical strength and predict the risk of fracture independent of BMD.…”

Section: Discussionmentioning

confidence: 99%

Association between COL1A1 gene polymorphisms and bone size in Caucasians

et al. 2004

View full text Add to dashboard Cite

Bone size is an important determinant of bone strength and a risk factor of osteoporotic fracture. Several studies indicate that bone size has a high heritability. Thus, a better understanding of genetic factors regulating bone size might have important clinical implications. In the present study, we examined the relationship between the collagen type I alpha 1 (COL1A1) gene and bone size at the spine, hip and wrist in a sample of 1873 subjects of Caucasian origin from 405 nuclear families. Three single-nucleotide polymorphisms (SNPs) in the COL1A1 gene were analyzed. The minor allele frequencies were 15.4, 18.8, and 1.9% for SNP1, SNP2, and SNP3, respectively. Haplotypes were reconstructed based on the family information as well as marker genotypes using the program Genehunter. We did not find evidence of population stratification, within-family association, or linkage for either single SNPs or haplotypes at any skeletal site. Suggestive evidence of total association was observed for the wrist size at SNP2 (P ¼ 0.011). After adjusting age, sex, height, and weight, subjects with the T allele of SNP2 had, on average, 3.05% smaller wrist size than noncarriers. When the subjects were divided into families with only female offspring and families with male offspring only, similar total associations were found at the wrist size for SNP2 with P-values of 0.011 and 0.010, respectively. In conclusion, the COL1A1 gene may have some effects on bone size variation at the wrist, but not at the spine or hip in our Caucasian nuclear families.

show abstract

“…Indeed, several candidate genes and chromosomal regions have been identified as possibly involved in BMD determination [12,13,47]. As mentioned in the Introduction, despite consistently high heritability values of BMD in various studies [1], the findings regarding association and linkage are largely contradictory [16,17,48,49].…”

Section: Discussionmentioning

confidence: 99%

Transmission Disequilibrium Test for Hand Bone Mineral Density and 11q12-13 Chromosomal Segment

et al. 2002

View full text Add to dashboard Cite

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.

show abstract

Recent progress in understanding the genetic susceptibility to osteoporosis

Cited by 83 publications

References 54 publications

Gender and Race/Ethnicity Differences in Lead Dose Biomarkers

Gender and Race/Ethnicity Differences in Lead Dose Biomarkers

Association between COL1A1 gene polymorphisms and bone size in Caucasians

Transmission Disequilibrium Test for Hand Bone Mineral Density and 11q12-13 Chromosomal Segment

Contact Info

Product

Resources

About