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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Association of Interleukin 10 Haplotype with Low Bone Mineral Density in Korean Postmenopausal Women

  • Park, Byung-Lae (Department of Genetic Epidemiology, SNP Genetics, Inc.) ;
  • Han, In-Kwon (Department of Internal Medicine, School of Medicine, SungKyunKwan University, Samsung Cheil Hospital) ;
  • Lee, Ho-Sa (Department of Biology, Research Institute of Basic Science, Kyung Hee University) ;
  • Kim, Lyoung-Hyo (Department of Genetic Epidemiology, SNP Genetics, Inc.) ;
  • Kim, Sa-Jin (Department of Obstetrics & Gynecology, College of Medicine, The Catholic University of Korea) ;
  • Shin, Joon-Shik (Institute Hospital of Jaseng Oriental Medicine & Jaseng-Bio Corp.) ;
  • Kim, Shin-Yoon (Department of Orthopedic Surgery, Skeletal Disease Genome Research Center, Kyungpook National University hospital) ;
  • Shin, Hyoung-Doo (Department of Genetic Epidemiology, SNP Genetics, Inc.)
  • Published : 2004.11.30
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Abstract

Osteoporosis is a disease characterized by exaggerated loss of bone mass, with as much as 50 to 85% of the variation in bone mineral density (BMD) commonly accepted as being genetically determined. Although intensive studies have attempted to elucidate the genetic effects of polymorphisms on BMD and/or osteoporosis in several genes, the genes involved are still largely unknown. The possible associations of genetic variants in five-candidate genes (IL10, CCR3, MCP1, MCP2 and GC) with spinal BMD were investigated in Korean postmenopausal women (n = 370). Fourteen SNPs in five candidate genes were genotyped, and the haplotypes of each gene constructed. The associations of adjusted spinal BMD by age, year since menopause (YSM) and body mass index (BMI), with genetic polymorphisms, were analyzed using multiple regression models. Genetic association analysis of Korean postmenopausal women revealed that IL10 -592A > C and/or IL10 ht2 were associated with decreased bone mass, whereas no significant associations were observed with all polymorphisms in other genes. The levels of spinal BMD in individuals bearing the IL10 -592CC genotype were lower ($0.78{\pm}0.16$) than those in others ($0.85{\pm}0.17$) (P = 0.02), and the BMD of IL10 ht2 bearing individuals were also lower ($0.82{\pm}0.15$) than those in others ($0.85{\pm}0.17$) (P = 0.04). Our results suggest that variants of IL10 might play a role in the decreased BMD, although additional study might need to be followed-up in a more powerful cohort.

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References

  1. Adebanjo, O. A., Moonga, B. S., Haddad, J. G., Huang, C. L. and Zaidi, M. (1998) A possible new role for vitamin D-binding protein in osteoclast control: inhibition of extracellular $Ca^{2+}$ sensing at low physiological concentrations. Biochem. Biophys. Res. Commun. 249, 668-671. https://doi.org/10.1006/bbrc.1998.9037
  2. Arden, N. K. and Spector, T. D. (1997) Genetic influences on muscle strength, lean body mass, and bone mineral density: a twin study. J. Bone Miner. Res. 12, 2076-2081. https://doi.org/10.1359/jbmr.1997.12.12.2076
  3. Arko, B., Prezelj, J., Komel, R., Kocijancic, A., Hudler, P. and Marc, J. (2002) Sequence variations in the osteoprotegerin gene promoter in patients with postmenopausal osteoporosis. J. Clin. Endocrinol. Metab. 87, 4080-4084. https://doi.org/10.1210/jc.2002-020124
  4. Asseman, C. and Powrie, F. (1998) Interleukin 10 is a growth factor for a population of regulatory T cells. Gut 42, 157-158. https://doi.org/10.1136/gut.42.2.157
  5. Combadiere, C., Ahuja, S. K. and Murphy, P. M. (1995) Cloning and functional expression of a human eosinophil CC chemokine receptor. J. Biol. Chem. 270, 16491-16494. https://doi.org/10.1074/jbc.270.28.16491
  6. Crawley, E., Kay, R., Sillibourne, J., Patel, P., Hutchinson, I. and Woo, P. (1999) Polymorphic haplotypes of the interleukin-10 5' flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis. Arthritis Rheum. 42, 1101-1108. https://doi.org/10.1002/1529-0131(199906)42:6<1101::AID-ANR6>3.0.CO;2-Y
  7. de Waal Malefyt, R., Yssel, H., Roncarolo, M. G., Spits, H. and de Vries, J. E. (1992) Interleukin-10. Curr. Opin. Immunol. 4, 314-320. https://doi.org/10.1016/0952-7915(92)90082-P
  8. Edwards-Smith, C. J., Jonsson, J. R., Purdie, D. M., Bansal, A., Shorthouse, C. and Powell, E. E. (1999) Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis C to interferon alfa. Hepatology 30, 526-530. https://doi.org/10.1002/hep.510300207
  9. Eisman, J. A. (1999) Genetics of osteoporosis. Endocr. Rev. 20, 788-804. https://doi.org/10.1210/er.20.6.788
  10. Eriksson, C., Eneslatt, K., Ivanoff, J., Rantapaa-Dahlqvist, S. and Sundqvist, K. G. (2003) Abnormal expression of chemokine receptors on T-cells from patients with systemic lupus erythematosus. Lupus 12, 766-774. https://doi.org/10.1191/0961203303lu467oa
  11. Eskdale, J., McNicholl, J., Wordsworth, P., Jonas, B., Huizinga, T., Field, M. and Gallagher, G. (1998) Interleukin-10 microsatellite polymorphisms and IL-10 locus alleles in rheumatoid arthritis susceptibility. Lancet 352, 1282-1283. https://doi.org/10.1016/S0140-6736(05)70489-X
  12. Fukunaga, K., Asano, K., Mao, X. Q., Gao, P. S., Roberts, M. H., Oguma, T., Shiomi, T., Kanazawa, M., Adra, C. N., Shirakawa, T., Hopkin, J. M. and Yamaguchi, K. (2001) Genetic polymorphisms of CC chemokine receptor 3 in Japanese and British asthmatics. Eur. Respir. J. 17, 59-63. https://doi.org/10.1183/09031936.01.17100590
  13. Garcia-Giralt, N., Nogues, X., Enjuanes, A., Puig, J., Mellibovsky, L., Bay-Jensen, A., Carreras, R., Balcells, S., Diez-Perez, A. and Grinberg, D. (2002) Two new single-nucleotide polymorphisms in the COL1A1 upstream regulatory region and their relationship to bone mineral density. J. Bone Miner. Res. 17, 384-393. https://doi.org/10.1359/jbmr.2002.17.3.384
  14. Garcia-Zepeda, E. A., Combadiere, C., Rothenberg, M. E., Sarafi, M. N., Lavigne, F., Hamid, Q., Murphy, P. M. and Luster, A. D. (1996) Human monocyte chemoattractant protein (MCP)-4 is a novel CC chemokine with activities on monocytes, eosinophils, and basophils induced in allergic and nonallergic inflammation that signals through the CC chemokine receptors (CCR)-2 and -3. J. Immunol. 157, 5613-5626.
  15. Groux, H., O'Garra, A., Bigler, M., Rouleau, M., Antonenko, S., de Vries, J. E. and Roncarolo, M. G. (1997) A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389, 737-742. https://doi.org/10.1038/39614
  16. Grove, J., Daly, A. K., Bassendine, M. F., Gilvarry, E. and Day, C. P. (2000) Interleukin 10 promoter region polymorphisms and susceptibility to advanced alcoholic liver disease. Gut 46, 540- 545. https://doi.org/10.1136/gut.46.4.540
  17. Heath, H., Qin, S., Rao, P., Wu, L., LaRosa, G., Kassam, N., Ponath, P. D. and Mackay, C. R. (1997) Chemokine receptor usage by human eosinophils. The importance of CCR3 demonstrated using an antagonistic monoclonal antibody. J. Clin. Invest. 99, 178-184. https://doi.org/10.1172/JCI119145
  18. Hedrick, P. and Kumar, S. (2001) Mutation and linkage disequilibrium in human mtDNA. Eur. J. Hum. Genet. 9, 969- 972.
  19. Hedrick, P. W. (1987) Gametic disequilibrium measures: proceed with caution. Genetics 117, 331-341.
  20. Hellier, S., Frodsham, A. J., Hennig, B. J., Klenerman, P., Knapp, S., Ramaley, P., Satsangi, J., Wright, M., Zhang, L., Thomas, H. C., Thursz, M. and Hill, A. V. (2003) Association of genetic variants of the chemokine receptor CCR5 and its ligands, RANTES and MCP-2, with outcome of HCV infection. Hepatology 38, 1468-1476. https://doi.org/10.1053/jhep.2003.09027
  21. Helminen, M. E., Kilpinen, S., Virta, M. and Hurme, M. (2001) Susceptibility to primary Epstein-Barr virus infection is associated with interleukin-10 gene promoter polymorphism. J. Infect. Dis. 184, 777-780. https://doi.org/10.1086/322987
  22. Howell, W. M., Turner, S. J., Bateman, A. C. and Theaker, J. M. (2001) IL-10 promoter polymorphisms influence tumour development in cutaneous malignant melanoma. Genes Immun. 2, 25-31. https://doi.org/10.1038/sj.gene.6363726
  23. Kanis, J. A., Melton, L. J. 3rd, Christiansen, C., Johnston, C. C. and Khaltaev, N. (1994) The diagnosis of osteoporosis. J. Bone Miner. Res. 9, 1137-1141.
  24. Keen, R. W., Woodford-Richens, K. L., Lanchbury, J. S. and Spector, T. D. (1998) Allelic variation at the interleukin-1 receptor antagonist gene is associated with early postmenopausal bone loss at the spine. Bone 23, 367-371. https://doi.org/10.1016/S8756-3282(98)00109-4
  25. Kim, M. H., Kim, H. J., Choi, J. Y. and Nahm, D. S. (2003) Transforming growth factor-beta3 gene SfaN1 polymorphism in Korean nonsyndromic cleft lip and palate patients. J. Biochem. Mol. Biol. 36, 533-537. https://doi.org/10.5483/BMBRep.2003.36.6.533
  26. Kobayashi, S., Inoue, S., Hosoi, T., Ouchi, Y., Shiraki, M. and Orimo, H. (1996) Association of bone mineral density with polymorphism of the estrogen receptor gene. J. Bone Miner. Res. 11, 306-311.
  27. Moore, K. W., O'Garra, A., de Waal Malefyt, R., Vieira, P. and Mosmann, T. R. (1993) Interleukin-10. Annu. Rev. Immunol. 11, 165-190. https://doi.org/10.1146/annurev.iy.11.040193.001121
  28. Morrison, N. A., Qi, J. C., Tokita, A., Kelly, P. J., Crofts, L., Nguyen, T. V., Sambrook, P. N. and Eisman, J. A. (1994) Prediction of bone density from vitamin D receptor alleles. Nature 367, 284-287. https://doi.org/10.1038/367284a0
  29. Morrison, N. A., Yeoman, R., Kelly, P. J. and Eisman, J. A. (1992) Contribution of trans-acting factor alleles to normal physiological variability: vitamin D receptor gene polymorphism and circulating osteocalcin. Proc. Natl. Acad. Sci. USA 89, 6665-6669. https://doi.org/10.1073/pnas.89.15.6665
  30. Murray, R. E., McGuigan, F., Grant, S. F., Reid, D. M. and Ralston, S. H. (1997) Polymorphisms of the interleukin-6 gene are associated with bone mineral density. Bone 21, 89-92. https://doi.org/10.1016/S8756-3282(97)00081-1
  31. Owens, J. M., Gallagher, A. C. and Chambers, T. J. (1996) IL-10 modulates formation of osteoclasts in murine hemopoietic cultures. J. Immunol. 157, 936-940.
  32. Rapado, A., Hawkins, F., Sobrinho, L., Diaz-Curiel, M., Galvao- Telles, A., Arver, S., Melo Gomes, J., Mazer, N., Garcia e Costa, J., Horcajada, C., Lopez-Gavilanes, E., Mascarenhas, M., Papapietro, K., Lopez Alvarez, M. B., Pereira, M. C., Martinez, G., Valverde, I., Garcia, J. J., Carballal, J. J. and Garcia, I. (1999) Bone mineral density and androgen levels in elderly males. Calcif. Tissue Int. 65, 417-421. https://doi.org/10.1007/s002239900726
  33. Redpath, S., Ghazal, P. and Gascoigne, N. R. (2001) Hijacking and exploitation of IL-10 by intracellular pathogens. Trends Microbiol. 9, 86-92. https://doi.org/10.1016/S0966-842X(00)01919-3
  34. Rees, L. E., Wood, N. A., Gillespie, K. M., Lai, K. N., Gaston, K. and Mathieson, P. W. (2002) The interleukin-10-1082 G/A polymorphism: allele frequency in different populations and functional significance. Cell Mol. Life Sci. 59, 560-569. https://doi.org/10.1007/s00018-002-8448-0
  35. Roth, I., Corry, D. B., Locksley, R. M., Abrams, J. S., Litton, M. J. and Fisher, S. J. (1996) Human placental cytotrophoblasts produce the immunosuppressive cytokine interleukin 10. J. Exp. Med. 184, 539-548. https://doi.org/10.1084/jem.184.2.539
  36. Schunck, B., Kraft, W. and Truyen, U. (1995) A simple touchdown polymerase chain reaction for the detection of canine parvovirus and feline panleukopenia virus in feces. J. Virol. Methods 55, 427-433. https://doi.org/10.1016/0166-0934(95)00069-3
  37. Shin, H. D., Winkler, C., Stephens, J. C., Bream, J., Young, H., Goedert, J. J., O'Brien, T. R., Vlahov, D., Buchbinder, S., Giorgi, J., Rinaldo, C., Donfield, S., Willoughby, A., O'Brien, S. J. and Smith, M. W. (2000) Genetic restriction of HIV-1 pathogenesis to AIDS by promoter alleles of IL10. Proc. Natl. Acad. Sci. USA 97, 14467-14472. https://doi.org/10.1073/pnas.97.26.14467
  38. Slemenda, C. W., Christian, J. C., Williams, C. J., Norton, J. A. and Johnston, C. C. Jr. (1991) Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates. J. Bone Miner. Res. 6, 561-567.
  39. Stanczuk, G. A., Sibanda, E. N., Perrey, C., Chirara, M., Pravica, V., Hutchinson, I. V. and Tswana, S. A. (2001) Cancer of the uterine cervix may be significantly associated with a gene polymorphism coding for increased IL-10 production. Int. J. Cancer. 94, 792-794. https://doi.org/10.1002/ijc.1543
  40. Stephens, M., Smith, N. J. and Donnelly, P. (2001) A new statistical method for haplotype reconstruction from population data. Am. J. Hum. Genet. 68, 978-989. https://doi.org/10.1086/319501
  41. Stewart, T. L. and Ralston, S. H. (2000) Role of genetic factors in the pathogenesis of osteoporosis. J. Endocrinol. 166, 235-245. https://doi.org/10.1677/joe.0.1660235
  42. Szalai, C., Kozma, G. T., Nagy, A., Bojszko, A., Krikovszky, D., Szabo, T. and Falus, A. (2001) Polymorphism in the gene regulatory region of MCP-1 is associated with asthma susceptibility and severity. J. Allergy Clin. Immunol. 108, 375-381. https://doi.org/10.1067/mai.2001.117930
  43. Turner, D. M., Williams, D. M., Sankaran, D., Lazarus, M., Sinnott, P. J. and Hutchinson, I. V. (1997) An investigation of polymorphism in the interleukin-10 gene promoter. Eur. J. Immunogenet. 24, 1-8. https://doi.org/10.1111/j.1365-2370.1997.tb00001.x
  44. Van Vlasselaer, P., Borremans, B., Van Den Heuvel, R., Van Gorp, U. and de Waal Malefyt, R. (1993) Interleukin-10 inhibits the osteogenic activity of mouse bone marrow. Blood 82, 2361-2370.
  45. Van Vlasselaer, P., Borremans, B., van Gorp, U., Dasch, J. R. and De Waal-Malefyt, R. (1994) Interleukin 10 inhibits transforming growth factor-beta (TGF-beta) synthesis required for osteogenic commitment of mouse bone marrow cells. J. Cell Biol. 124, 569-577. https://doi.org/10.1083/jcb.124.4.569
  46. Vidigal, P. G., Germer, J. J. and Zein, N. N. (2002) Polymorphisms in the interleukin-10, tumor necrosis factoralpha, and transforming growth factor-beta1 genes in chronic hepatitis C patients treated with interferon and ribavirin. J. Hepatol. 36, 271-277.
  47. Vreeland, W. N., Meagher, R. J. and Barron, A. E. (2002) Multiplexed, high-throughput genotyping by single-base extension and end-labeled free-solution electrophoresis. Anal. Chem. 74, 4328-4333. https://doi.org/10.1021/ac0258094
  48. Wanidworanun, C. and Strober, W. (1993) Predominant role of tumor necrosis factor-alpha in human monocyte IL-10 synthesis. J. Immunol. 151, 6853-6861.
  49. Wu, M. S., Huang, S. P., Chang, Y. T., Shun, C. T., Chang, M. C., Lin, M. T., Wang, H. P. and Lin, J. T. (2002) Tumor necrosis factor-alpha and interleukin-10 promoter polymorphisms in Epstein-Barr virus-associated gastric carcinoma. J. Infect. Dis. 185, 106-109. https://doi.org/10.1086/324771
  50. Yamada, Y., Miyauchi, A., Takagi, Y., Tanaka, M., Mizuno, M. and Harada, A. (2001) Association of the C-509-->T polymorphism, alone of in combination with the T869-->C polymorphism, of the transforming growth factor-beta1 gene with bone mineral density and genetic susceptibility to osteoporosis in Japanese women. J. Mol. Med. 79, 149-156. https://doi.org/10.1007/s001090100190
  51. Yee, L. J., Tang, J., Gibson, A. W., Kimberly, R., Van Leeuwen, D. J. and Kaslow, R. A. (2001) Interleukin 10 polymorphisms as predictors of sustained response in antiviral therapy for chronic hepatitis C infection. Hepatology 33, 708-712. https://doi.org/10.1053/jhep.2001.22347
  52. Young, D., Hopper, J. L., Nowson, C. A., Green, R. M., Sherwin, A. J., Kaymakci, B., Smid, M., Guest, C. S., Larkins, R. G. and Wark, J. D. (1995) Determinants of bone mass in 10- to 26-year-old females: a twin study. J. Bone Miner. Res. 10, 558- 567.
  53. Zhang, J., Chen, H., Hu, L., Fu, J., Zhang, H. and Chen, Y. (2002) Correlation between polymorphism of IL-4 and IL-10 gene promoter and childhood asthma and their impact upon cytokine expression. Zhonghua Yi Xue Za Zhi 82, 114-118.
  54. Zhang, J. and Li, K. (2003) On-off regulation of 3' exonuclease excision to DNA polymerization by Exo+ polymerase. J. Biochem. Mol. Biol. 36, 525-528. https://doi.org/10.5483/BMBRep.2003.36.6.525
  55. Zheng, C., Huang, D., Liu, L., Wu, R., Bergenbrant Glas, S., Osterborg, A., Bjorkholm, M., Holm, G., Yi, Q. and Sundblad, A. (2001) Interleukin-10 gene promoter polymorphisms in multiple myeloma. Int. J. Cancer 95, 184-188. https://doi.org/10.1002/1097-0215(20010520)95:3<184::AID-IJC1031>3.0.CO;2-V

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