Современные подходы к выявлению генетических предикторов остеопороза

А. П. Шепелькевич, Ю. В. Дыдышко УО «Белорусский государственный медицинский университет»

2014 №3 | Лекции

Аннотация

Список литературы

Остеопороз (ОП) – это заболевание, характеризующееся снижением минеральной плотности кости (МПК) и повышенным риском переломов, является результатом сложного взаимодействия между факторами окружающей среды и генетической детерминантой. Исследования по изучению роли наследственности показали, что МПК, ультразвуковые характеристики, состояние скелетной геометрии и метаболизма костной ткани, имеют значимую наследственную предрасположенность.

Ключевые слова:

остеопороз, одиночные нуклеотидные полиморфизмы, костная ткань, минеральная плотность кости, переломы

Modern approaches to identification of genetic predictors of osteoporosis

Osteoporosis, which is characterized by reduced bone mineral density (BMD)and an increased risk of fragility fractures, is the result of a complex interaction between environmental factors and genetic variants that confer susceptibility. Heritability studies have shown that BMD and other osteoporosisrelated traits such as ultrasound properties of bone, skeletal geometry and bone turnover have significant inheritable components. Further meta-analyses of genome-wide association studies (GWAS) data and deep resequencing of rare variants will uncover more novel susceptibility loci and ultimately provide possible therapeutic targets for fracture prevention.

Keywords

osteoporosis, single nucleotide polymorphisms, bone tissue, bone mineral density, fractures

1. Arden, N. K. The her ita bility of bone mineral density, ultra sound of the calca neus and hip axis le ngth: a study of po stmenopa usal twins / N. K. Arden [et al .] // Journal of Bone and Mineral Researc h. – 1996. – N 11 . – P. 530–534.
2. Bodmer, W. Common and rare var iants in mult ifac - tor ial suscept ibility to co mmon diseases / W. Bodmer , C. Bonilla // J. Nat ure Ge net ics. – 2008. – N 40. – P. 695–701.
3. Burge, R. Incidence and eco nomic burden of osteo - poro sis-relate d fract ure s in the Unite d States, 2005– 2025 / R. Burge [et al .] // J of Bone and Mineral Researc h. – 2007. – N 22. – P. 465–475.
4. Chakravarti, A. Nat ure , nurt ure and human disea se / A. Chakra vart i, P. Little // J. Nat ure . – 2003. – N 421. – P. 412–414.
5. Cirulli, E. T. and Gol dste in, D. B. (2010) Unco ver ingthe role s of rare var iants in co mmon disea se thro ugh whole - genome sequencing. Nat ure Reviews. Ge net ics 11 , 415–425.
6. Duncan, E. L. et al . (2011 ) Ge nome-wide assoc iat ion study using extre me tr uncate select ion identifies novel genes affect ing bone mineral density and fract ure risk. PLoSenet 7, e1 001372.
7. Fang, Y. Vita min D binding prote in genot ype and osteoporo sis / Y. Fang [et al .] // J. Calc ified Tissue Inter national . – 2009. – N 85. – P. 85–93.
8. Greenspan, S. L. Effect of hor mone ere place ment, ale ndro nate , or co mbinat ion therap y on hip str uct ural geo metr y: a 3-year , double -blind, place bo-controlle d clinical trial / S. L. Gree nspa n [et al .] // Journal of Bone and Mineral Researc h. – 2005. – N 20. – P. 1525–1532.
9. Gueguen, R. Segre gat ion anal ysi sand var iance co mpo nents anal ysis of bone mineral density in healt hy families / R. Gueguen [et al .] // Journal of Bone and Mineral Researc h. – 1995. – N 10. – P. 2017 –2022.
10. Guo, Y. IL21R and PTH may underl ie var iat ion of femoral nec k bone mineral density as re veale d by a genome-wide assoc iat ion study / Y. Guo [et al .] // Journal of Bone and Mineral Researc h. – 2010. – N 25. – P. 1042–1048.
11. Hindorff, L. A. Pote ntial et iolo gic and funct ional impl icat ions of genome-wide assoc iat ion loc i for human disea ses and tra it / L. A. Hindor ff [et al .] // Procee dings of the Nat ional Aca demy of Science s of the Unite d State s of Amer ica . – 2009. – N 106. – P. 9362–9367.
12. Ioannidis, J. P. Meta -anal ysis of genome wide sca ns pro vides evidence for sex and site spec ific re gulat ion of bone mass / J. P. Ioa nnidis [et al .] (2007) Journal of Bone and Mineral Researc h 22, 17 3–183.
13. Kanis, J. A. Assessment of osteoporo sis at the pr imar y healt h-care le vel / J. A. Kanis on behal f of the Worl d Healt h Organizat ion Scientific Gro up – Univer sity of Sheffiel d, Unite d Kindom, 2007. – 287 p.
14. Kaptoge, S. Pre dict ion of incident hip fract ure risk by femur geo metr y var iable s mea sure d by hip str uct ural anal ysis in the study of osteoporot ic fract ure s / S. Kapto ge [et al .] // Journal of Bone and Mineral Researc h. – 2008. – N 23. – P. 1892–1904.
15. Kiel, D. P. Ge nome-wide assoc iat ion with bone mass and geo metr y in the Fra mingham Heart Study / D. P. Kiel [et al .] // BMC Medical Ge net ics. – 2007. – N 8, Suppl 1. – S. 14.
16. Kou, I. et al . (2011 ) Common var iants in a novel gene, FONG on chro mosome 2q33.1 co nfer risk of osteoporosis in Japa nese. PLoS One 6, e1 9641.
17 . Kruglyak, L. The roa d to genome-wide association studies / L. Kruglyak // J. Nat ure Reviews. Ge net ics. – 2008. – N 9. – P. 314–318.
18. Lai, B. M. Estro gen receptor alp ha CA dinucleot ide repeat pol ymorp hism is assoc iate d with rate of bone lo ss in per imenopa usal women and bone mineral density and risk of osteoporot ic fract ure s in po stmenopa usal women / B. M. Lai [et al .] // J. Osteoporosis Inter nat ional . – 2008. – N 19. – P. 571 –579.
19. Liu, Y. Z. et al . (2008) Identificat ion of PLCL1 gene for hip bone size var iat ion in female s in a genome-wide assoc iat ion study. PLoS One 3, e3160
20. Manolio, T. A. Finding the missing her ita bility of co mple x disea ses / T. A. Manol io [et al .] // J. Nat ure . – N 461. – P. 747–753.
21. Manolio, T. A. Ge nes, enviro nment, healt h, and disea se: fac ing up to co mple xity / T. A. Manol io, F. S. Coll ins // J. Human Here dity. – 2007. – N 63. – P. 63–66.
22. Moffett, S. P. Assoc iat ion of the VDR translation start site pol ymorp hism and fract ure risk in ol der women / S. P. Moffett [et al .] // Journal of Bone and Mineral Researc h. – 2007. – N 22. – P. 730–736.
23. Mullin, B. H. Furt her genet ic evidence suggesting a role for the RhoG TPase-RhoG EFpat hway in osteoporo sis / B. H. Mull in [et al .] // J. Bone. – 2009. – N 45. – P. 387–391.
24. Mullin, B. H. Identificat ion of a role for the ARHGEF3 gene in po stmenopa usal osteoporo sis / B. H. Mull in [et al .] // America n Journal of Human Ge net ics. – 2008. – N 82. – P. 1262–1269.
25. Ng, M. Y. Effect of enviro nmental factor sand gender on the her ita bility of bone mineral density and bone size / M. Y. Ng [et al .] // Annal s of Human Ge net ics. – 2006. – N 70. – P. 428–438.
26. Peacock, M. Sex-spec ific quantitat ive tra it loc I co ntr ibute to nor mal var iat ion in bone str uct ure at the pro ximal femur in men / M. Peacoc k [et al .] // J. Bone. – 2005. – N 37. – P. 467–473.
27. Riancho, J. A. Assoc iat ion of the aro mata se gene allele s with BMD: ep idemiolo gical and funct ional evidence / J. A. Riancho [et al .] // Journal of Bone and Mineral Researc h. – 2009. – N 24. – P. 17 09–171 8.
28. Riancho, J. A. MTHFR pol ymorp hism and bone mineral density: meta -anal ysis of published studies / J. A. Riancho, C. Valero , M. T. Zarra beitia // J. Calc ified Tissue Inter nat ional . – 2006. – N 79. – P. 289–293.
29. Richards, J. B. Bone mineral density, osteoporo sis, and osteoporot ic fract ure s: a genome-wide assoc iat ion study / J. B. Richar ds [et al .] // J. Lancet . – 2008. – N 371 . – P. 1505–1512.
30. Richards, J. B. Colla borat ive metaa nal ysis: assoc iat ions of 150 ca ndidate genes with osteoporo sis and osteoporot ic fract ure / J. B. Richar ds [et al .] // Annal s of Inter nal Medicine. – 2009. – N 151. – P. 528–537.
31. Rivadeneira, F. Estro gen receptor beta (ESR2) po - lymorp hisms in interact ion with estro gen receptor alp ha (ESR1) and insulin-like gro wth factor I (IGF1) var iants influence the risk of fract ure in po stmenopa usal women / F. Rivadeneira [et al .] // Journal of Bone and Mineral Researc h. – 2006. – N 21. – P. 1443–1456.
32. Rivadeneira, F. Twenty bone-mineral density loc I identified by lar ge-scale meta -anal ysis of genome-wide assoc iat ion studies / F. Rivadeneira [et al .] // J. Nature Ge net ics. – 2009. – N 41. – P. 11 99–1206.
33. Sigurdsson, G. Impact of genet ics on lo w bone mass in adult s / G. Sigurdsson [et al .] // Journal of Bone and Mineral Researc h. – 2008. – N 23. – P. 1584–1590.
34. Sims, A. M. Ge net ic anal yses in a sample of individual s with high or lo w BMD shows assoc iat ion with mult iple Wnt pat hway genes / A. M. Sims [et al .] // Journal of Bone and Mineral Researc h. – 2008. – N 23. – P. 499–506.
35. Styrkarsdottir, U. New sequence var iants assoc iate d with bone mineral density / U. Styrkar sdott ir [et al .] // J. Nat ure Ge net ics. –2009. – N 41. – P. 15–17 .
36. Wilson, S. G. A genome-scree n of a lar ge twin co hort re veal s linkage for quantitat ive ultra sound of the calca neus to 2q33–37 and 4q12–21 / S. G. Wilson [et al .] // Journal of Bone and Mineral Researc h. – 2004. – N 19. – P. 270–277 .
37. Wilson, S. G. Common sequence var iat ion in FLNB re gulate s bone str uct ure in women in the general pop ulation and FLNB mRNA expre ssion in osteo bla sts in vitro / S. G. Wilson [et al .] // Journal of Bone and Mineral Researc h. – 2009. – N 24. – P. 1989–1997.
38. Yazdanpanah, N. The 1997 G/Tand Sp1pol ymorphisms in the colla gen type I alp ha1 (COLIA1) gene in relation to changes in femoral nec k bone mineral density and the risk of fract ure in the el derl y: the Rotter dam study / N. Yazdanpa nah [et al .] // J. Calc ified Tissue Inter nat ional . – 2007. – N 81. – P. 18–25.
39. Yerges, L. M. High-density assoc iat ion study of 383 ca ndidate genes for vol umetr ic BMD at the femoral nec k and lumbar spine among ol der men / L. M. Yer ges [et al .] // Journal of Bone and Mineral Researc h. – 2009. – N 24. – P. 2039–2049.
40. Zhao, L. J. Ge nome-wide assoc iat ion study for femoral nec k bone geo metr y / L. J. Zhao [et al .] // Journal of Bone and Mineral Researc h. – 2010. – N 25. – P. 320–329.