Decreased Bone Mineral Density in Subjects Carrying Familial Defective Apolipoprotein B-100
Context: Although numerous epidemiologic studies have documented associations between osteoporosis and cardiovascular disease, the mechanisms underlying this association remain to be clarified. One hypothesis is that hyperlipidemia may be a common predisposing factor to both atherosclerotic heart di...
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Published in | The journal of clinical endocrinology and metabolism Vol. 98; no. 12; pp. E1999 - E2005 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Endocrine Society
01.12.2013
Copyright by The Endocrine Society |
Subjects | |
Online Access | Get full text |
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Summary: | Context:
Although numerous epidemiologic studies have documented associations between osteoporosis and cardiovascular disease, the mechanisms underlying this association remain to be clarified. One hypothesis is that hyperlipidemia may be a common predisposing factor to both atherosclerotic heart disease and bone fragility.
Objective:
To evaluate this, we compared bone mineral density (BMD) between subjects with and without the R3500Q APOB mutation, the cause of familial defective apolipoprotein B-100, which has been previously shown to markedly increase low-density lipoprotein cholesterol (LDL-C). We hypothesized that R3500Q carriers would have lower BMD due to lifetime, elevated LDL-C.
Design:
This was a a cross-sectional study in the Old Order Amish (OOA) population.
Participants:
The R3500Q APOB mutation is present at a high frequency (∼6% vs <0.5%) in the OOA population due to a founder effect. Therefore, we conducted analysis on 1097 Amish individuals of whom 125 were R3500Q carriers.
Main Outcome Measure:
BMD was measured by dual-energy x-ray absorptiometry.
Results:
After adjusting for age, age2, sex, body mass index, and family structure, carriers for the Q risk allele had significantly lower BMD than noncarriers at the femoral neck (P = .037), lumbar spine (P = .035) and whole body (P = .016). Adjusting for LDL-C attenuated the association between R3500Q genotype and BMD but did not completely explain the relationship. Subgroup analyses showed no significant interactions with sex, age, or presence of metabolic syndrome.
Conclusion:
These results use the unique genetic architecture of the OOA population to provide a novel line of evidence supporting a causal role for elevated LDL-C in lowering BMD. |
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Bibliography: | This work was supported by Research Grants R01-HL088119, R01-HL069313, R01-AR046838, U01-HL072515, U01-GM074518–04, and U01-HL105198 from the National Institutes of Health (NIH), Scientist Development Grant 0830146N (to H.S.) and Grant-in-Aid 0855400E (to B.D.M.) from the American Heart Association. L.M.Y.-A. was supported by F32 AR059469 from National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH. Partial support was also received from the Mid-Atlantic Nutrition and Obesity Center (P30 DK072488). Construction and maintenance of the Anabaptist Genealogy Database is covered under an Institutional Review Board-approved protocol at the NIH (Dr Leslie Biesecker, Principal Investigator). ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0021-972X 1945-7197 |
DOI: | 10.1210/jc.2013-2471 |