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Modulation of Bone Mineral Density and Its Response to Menopausal Hormone Therapy according to the Apolipoprotein E Genotype in Postmenopausal Korean Women

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Objectives: Genetic factors are a major cause of osteoporosis. The present study evaluated the association of the apolipoprotein E (ApoE) genotype with bone mineral density (BMD) and its response to menopausal hormone therapy (MHT) in postmenopausal Korean women.Methods: This retrospective cohort study included 172 postmenopausal women with no endocrine diseases, medications, or lifestyles that would affect bone metabolism and who were continuously treated with MHT for at least 2 years. BMDs were measured at baseline and periodically.Results: Linear regression analysis demonstrated similar baseline BMDs at the lumbar spine, but significantly lower at the femur neck and total hip in the ApoE ε4 carrier than in the noncarrier group, after controlling for age, body mass index, and history of MHT usage. Overall, the Wilcoxon signed rank test demonstrated that MHT increased the BMD percentage change at all three regions, and the Generalized Estimating Equation (GEE) demonstrated significant time trends at the lumbar spine and femur neck. ApoE ε4 noncarriers exhibited a significant time trend in BMD changes at the femur neck, whereas ε4 carriers exhibited a time trend at the lumbar spine. However, BMD changes at each time point were comparable at all regions between the groups. Notably, GEE adjusted for baseline characteristics and BMD revealed a significant interaction effect of time and ApoE ε4 allele in BMD changes at the femur neck.Conclusions: Postmenopausal Korean women carrying the ApoE ε4 allele demonstrated a lower hip BMD compared with ε4 noncarriers. Furthermore, the ε4 allele may modulate hip BMD responses to MHT.

Abstract

Objectives: Genetic factors are a major cause of osteoporosis. The present study evaluated the association of the apolipoprotein E (ApoE) genotype with bone mineral density (BMD) and its response to menopausal hormone therapy (MHT) in postmenopausal Korean women.Methods: This retrospective cohort study included 172 postmenopausal women with no endocrine diseases, medications, or lifestyles that would affect bone metabolism and who were continuously treated with MHT for at least 2 years. BMDs were measured at baseline and periodically.Results: Linear regression analysis demonstrated similar baseline BMDs at the lumbar spine, but significantly lower at the femur neck and total hip in the ApoE ε4 carrier than in the noncarrier group, after controlling for age, body mass index, and history of MHT usage. Overall, the Wilcoxon signed rank test demonstrated that MHT increased the BMD percentage change at all three regions, and the Generalized Estimating Equation (GEE) demonstrated significant time trends at the lumbar spine and femur neck. ApoE ε4 noncarriers exhibited a significant time trend in BMD changes at the femur neck, whereas ε4 carriers exhibited a time trend at the lumbar spine. However, BMD changes at each time point were comparable at all regions between the groups. Notably, GEE adjusted for baseline characteristics and BMD revealed a significant interaction effect of time and ApoE ε4 allele in BMD changes at the femur neck.Conclusions: Postmenopausal Korean women carrying the ApoE ε4 allele demonstrated a lower hip BMD compared with ε4 noncarriers. Furthermore, the ε4 allele may modulate hip BMD responses to MHT.

참고문헌 (31)

  1. Ralston SH, "Genetics of osteoporosis", Proc Nutr Soc, 66, pp.158~165 (2007)
  2. Deng HW, "Tests of linkage and", or association of genes for vitamin D receptor, osteocalcin, and parathyroid hormone with bone mineral density, 2002, pp.17, 678~686
  3. Seeman E, "Reduced bone mass in daughters of women with osteoporosis", N Engl J Med, 320, pp.554~558 (1989)
  4. Wang Y, "Gene-hormone therapy interaction and fracture risk in postmenopausal women", J Clin Endocrinol Metab, 102, pp.1908~1916 (2017)
  5. Lee SH, "Prediction of future osteoporotic fracture occurrence by genetic profiling : a 6-year follow-up observational study", J Clin Endocrinol Metab, 101, pp.1215~1224 (2016)
  6. Raulin AC, "ApoE in Alzheimerʼs disease : pathophysiology and therapeutic strategies", Mol Neurodegener, 17, pp.72~ (2022)
  7. Liu S, "Apolipoprotein E gene polymorphism and the risk of cardiovascular disease and type 2diabetes", BMC Cardiovasc Disord, 19, pp.213~ (2019)
  8. Shiraki M, "Association of bone mineral density with apolipoprotein E phenotype", J Bone Miner Res, 12, pp.1438~1445 (1997)
  9. Johnston JM, "APOE 4 and hip fracture risk in a community-based study of older adults", J Am Geriatr Soc, 47, pp.1342~1345 (1999)
  10. Weisgraber KH, "Human E apoprotein heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo-E isoforms", J Biol Chem, 256, pp.9077~9083 (1981)
  11. Peter I, "Associations of APOE gene polymorphisms with bone mineral density and fracture risk : a meta-analysis", Osteoporos Int, 22, pp.1199~1209 (2011)
  12. Hixson JE, "Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI", J Lipid Res, 31, pp.545~548 (1990)
  13. Dick IM, "Apolipoprotein E4 is associated with reduced calcaneal quantitative ultrasound measurements and bone mineral density in elderly women", Bone, 31, pp.497~502 (2002)
  14. Pluijm SM, "Effects of gender and age on the association of apolipoprotein E epsilon4 with bone mineral density, bone turnover and the risk of fractures in older people", Osteoporos Int, 13, pp.701~709 (2002)
  15. Cauley JA, "Apolipoprotein E polymorphism : a new genetic marker of hip fracture risk--The Study of Osteoporotic Fractures", J Bone Miner Res, 14, pp.1175~1181 (1999)
  16. Lee SI, "Association of apolipoprotein E polymorphism with bone mineral density in postmenopausal women with rheumatoid arthritis", Rheumatology (Oxford), 44, pp.1067~1068 (2005)
  17. Kim SA, "Association of APOE genotype with bone mineral density in men and women : The Dong-gu and Namwon studies", Chonnam Med J, 52, pp.59~63 (2016)
  18. Crandall CJ, "Presence of vasomotor symptoms is associated with lower bone mineral density : a longitudinal analysis", Menopause, 16, pp.239~246 (2009)
  19. Virolainen SJ, "Gene-environment interactions and their impact on human health", Genes Immun, 24, pp.1~11 (2023)
  20. "Effects of hormone therapy on bone mineral density: results from the postmenopausal estrogen", progestin interventions (PEPI) trial. The Writing Group for the PEPI, 1996, pp.276, 1389~1396
  21. Lindsay R, "Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women", JAMA, 287, pp.2668~2676 (2002)
  22. Jackson RD, "Effects of conjugated equine estrogen on risk of fractures and BMD in postmenopausal women with hysterectomy : results from the womenʼs health initiative randomized trial", J Bone Miner Res, 21, pp.817~828 (2006)
  23. Gerdes LU, "Regional and hormone-dependent effects of apolipoprotein E genotype on changes in bone mineral in perimenopausal women", J Bone Miner Res, 16, pp.1906~1916 (2001)
  24. Heikkinen AM, "Does apolipoprotein E genotype relate to BMD and bone markers in postmenopausal women?", Maturitas, 34, pp.33~41 (2000)
  25. Salamone LM, "Apolipoprotein E gene polymorphism and bone loss : estrogen status modifies the influence of apolipoprotein E on bone loss", J Bone Miner Res, 15, pp.308~314 (2000)
  26. Kohlmeier M, "Bone fracture history and prospective bone fracture risk of hemodialysis patients are related to apolipoprotein E genotype", Calcif Tissue Int, 62, pp.278~281 (1998)
  27. Niemeier A, "The role of apolipoprotein E in bone metabolism", Bone, 50, pp.518~524 (2012)
  28. Huang R, "Lowering circulating apolipoprotein E levels improves aged bone fracture healing", JCI Insight, 4, pp.e129144~ (2019)
  29. Noguchi T, "Apolipoprotein E plays crucial roles in maintaining bone mass by promoting osteoblast differentiation via ERK1", 2 pathway and by suppressing osteoclast differentiation via c-Fos, NFATc1, and NF-κB pathway, 2018, pp.503, 644~650
  30. Wang JM, "Activation of estrogen receptor alpha increases and estrogen receptor beta decreases apolipoprotein E expression in hippocampus in vitro and in vivo", Proc Natl Acad Sci U S A, 103, pp.16983~16988 (2006)
  31. Muesing RA, "Effects of unopposed conjugated equine estrogen on lipoprotein composition and apolipoprotein-E distribution", J Clin Endocrinol Metab, 75, pp.1250~1254 (1992)

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