Mutation analysis of WNT10B in obese children, adolescents and adults

详细信息    查看全文

• 作者：Jasmijn K. Van Camp (1)
  Doreen Zegers (1)
  Stijn L. Verhulst (2)
  Kim Van Hoorenbeeck (2)
  Guy Massa (3)
  An Verrijken (4)
  Kristine N. Desager (2)
  Luc F. Van Gaal (4)
  Wim Van Hul (1)
  Sigri Beckers (1)
  
• 关键词：Obesity ; WNT10B ; Mutation analysis ; Genetics
• 刊名：Endocrine
• 出版年：2013
• 出版时间：August 2013
• 年：2013
• 卷：44
• 期：1
• 页码：107-113
• 全文大小：210KB
• 参考文献：1. L.F. Van Gaal, I.L. Mertens, C.E. De Block, Mechanisms linking obesity with cardiovascular disease. Nature 444(7121), 875-80 (2006). doi:10.1038/nature05487 7">CrossRef
  2. P. Bhanot, M. Brink, C.H. Samos, J.C. Hsieh, Y. Wang, J.P. Macke, D. Andrew, J. Nathans, R. Nusse, A new member of the frizzled family from / Drosophila functions as a wingless receptor. Nature 382(6588), 225-30 (1996). doi:10.1038/382225a0 CrossRef
  3. J. Papkoff, M. Aikawa, WNT-1 and HGF regulate GSK3 beta activity and beta-catenin signaling in mammary epithelial cells. Biochem. Biophys. Res. Commun. 247(3), 851-58 (1998). doi:10.1006/bbrc.1998.8888 CrossRef
  4. J. Papkoff, B. Rubinfeld, B. Schryver, P. Polakis, Wnt-1 regulates free pools of catenins and stabilizes APC?catenin complexes. Mol. Cell. Biol. 16(5), 2128-134 (1996)
  5. A. Bejsovec, Wnt signaling: an embarrassment of receptors. Curr. Biol. 10(24), 919-22 (2000). doi:S0960-9822(00)00852-6 CrossRef
  6. S. Kang, C.N. Bennett, I. Gerin, L.A. Rapp, K.D. Hankenson, O.A. Macdougald, Wnt signaling stimulates osteoblastogenesis of mesenchymal precursors by suppressing CCAAT/enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma. J. Biol. Chem. 282(19), 14515-4524 (2007). doi:10.1074/jbc.M700030200 74/jbc.M700030200">CrossRef
  7. M. Kawai, S. Mushiake, K. Bessho, M. Murakami, N. Namba, C. Kokubu, T. Michigami, K. Ozono, Wnt/Lrp/beta-catenin signaling suppresses adipogenesis by inhibiting mutual activation of PPARgamma and C/EBPalpha. Biochem. Biophys. Res. Commun. 363(2), 276-82 (2007). doi:10.1016/j.bbrc.2007.08.088 7.08.088">CrossRef
  8. M. Fu, M. Rao, T. Bouras, C. Wang, K. Wu, X. Zhang, Z. Li, T.P. Yao, R.G. Pestell, Cyclin D1 inhibits peroxisome proliferator-activated receptor gamma-mediated adipogenesis through histone deacetylase recruitment. J. Biol. Chem. 280(17), 16934-6941 (2005). doi:10.1074/jbc.M500403200 74/jbc.M500403200">CrossRef
  9. S.O. Freytag, T.J. Geddes, Reciprocal regulation of adipogenesis by Myc and C/EBP alpha. Science 256(5055), 379-82 (1992) 79">CrossRef
  10. M. Okamura, H. Kudo, K. Wakabayashi, T. Tanaka, A. Nonaka, A. Uchida, S. Tsutsumi, I. Sakakibara, M. Naito, T.F. Osborne, T. Hamakubo, S. Ito, H. Aburatani, M. Yanagisawa, T. Kodama, J. Sakai, COUP-TFII acts downstream of Wnt/beta-catenin signal to silence PPARgamma gene expression and repress adipogenesis. Proc. Natl. Acad. Sci. USA 106(14), 5819-824 (2009). doi:10.1073/pnas.0901676106 73/pnas.0901676106">CrossRef
  11. K.A. Longo, W.S. Wright, S. Kang, I. Gerin, S.H. Chiang, P.C. Lucas, M.R. Opp, O.A. MacDougald, Wnt10b inhibits development of white and brown adipose tissues. J. Biol. Chem. 279(34), 35503-5509 (2004). doi:10.1074/jbc.M402937200 74/jbc.M402937200">CrossRef
  12. C.N. Bennett, S.E. Ross, K.A. Longo, L. Bajnok, N. Hemati, K.W. Johnson, S.D. Harrison, O.A. MacDougald, Regulation of Wnt signaling during adipogenesis. J. Biol. Chem. 277(34), 30998-1004 (2002). doi:10.1074/jbc.M204527200 74/jbc.M204527200">CrossRef
  13. C.N. Bennett, K.A. Longo, W.S. Wright, L.J. Suva, T.F. Lane, K.D. Hankenson, O.A. MacDougald, Regulation of osteoblastogenesis and bone mass by Wnt10b. Proc. Natl. Acad. Sci. U S A 102(9), 3324-329 (2005). doi:10.1073/pnas.0408742102 73/pnas.0408742102">CrossRef
  14. J.A. Kennell, O.A. MacDougald, Wnt signaling inhibits adipogenesis through beta-catenin-dependent and -independent mechanisms. J. Biol. Chem. 280(25), 24004-4010 (2005). doi:10.1074/jbc.M501080200 74/jbc.M501080200">CrossRef
  15. A.M. Vertino, J.M. Taylor-Jones, K.A. Longo, E.D. Bearden, T.F. Lane, R.E. McGehee Jr, O.A. MacDougald, C.A. Peterson, Wnt10b deficiency promotes coexpression of myogenic and adipogenic programs in myoblasts. Mol. Biol. Cell 16(4), 2039-048 (2005). doi:10.1091/mbc.E04-08-0720 720">CrossRef
  16. S.E. Ross, N. Hemati, K.A. Longo, C.N. Bennett, P.C. Lucas, R.L. Erickson, O.A. MacDougald, Inhibition of adipogenesis by Wnt signaling. Science 289(5481), 950-53 (2000) CrossRef
  17. W.S. Wright, K.A. Longo, V.W. Dolinsky, I. Gerin, S. Kang, C.N. Bennett, S.H. Chiang, T.C. Prestwich, C. Gress, C.F. Burant, V.S. Susulic, O.A. MacDougald, Wnt10b inhibits obesity in ob/ob and agouti mice. Diabetes 56(2), 295-03 (2007). doi:10.2337/db06-1339 7/db06-1339">CrossRef
  18. H. Taipaleenmaki, B.M. Abdallah, A. Aldahmash, A.M. Saamanen, M. Kassem, Wnt signalling mediates the cross-talk between bone marrow derived pre-adipocytic and pre-osteoblastic cell populations. Exp. Cell Res. 317(6), 745-56 (2010). doi:10.1016/j.yexcr.2010.12.015 CrossRef
  19. C. Christodoulides, A. Scarda, M. Granzotto, G. Milan, E. Dalla Nora, J. Keogh, G. De Pergola, H. Stirling, N. Pannacciulli, J.K. Sethi, G. Federspil, A. Vidal-Puig, I.S. Farooqi, S.O- Rahilly, R. Vettor, WNT10B mutations in human obesity. Diabetologia 49(4), 678-84 (2006). doi:10.1007/s00125-006-0144-4 7/s00125-006-0144-4">CrossRef
  20. S. Beckers, I. Mertens, A. Peeters, L. Van Gaal, W. Van Hul, Screening for melanocortin-4 receptor mutations in a cohort of Belgian morbidly obese adults and children. Int. J. Obes. (Lond) 30(2), 221-25 (2006). doi:10.1038/sj.ijo.0803126 CrossRef
  21. S. Beckers, D. Zegers, F. de Freitas, A.V. Peeters, S.L. Verhulst, G. Massa, L.F. Van Gaal, J.P. Timmermans, K.N. Desager, W. Van Hul, Identification and functional characterization of novel mutations in the melanocortin-4 receptor. Obesity facts 3(5), 304-11 (2010). doi:10.1159/000321565 CrossRef
  22. M. Roelants, R. Hauspie, K. Hoppenbrouwers, References for growth and pubertal development from birth to 21?years in Flanders. Belgium. Ann. Hum. Biol. 36(6), 680-94 (2009). doi:10.3109/03014460903049074 74">CrossRef
  23. S.A. Miller, D.D. Dykes, H.F. Polesky, A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 16(3), 1215 (1988) CrossRef
  24. P.C. Ng, S. Henikoff, Predicting deleterious amino acid substitutions. Genome Res. 11(5), 863-74 (2001). doi:10.1101/gr.176601 76601">CrossRef
  25. I.A. Adzhubei, S. Schmidt, L. Peshkin, V.E. Ramensky, A. Gerasimova, P. Bork, A.S. Kondrashov, S.R. Sunyaev, A method and server for predicting damaging missense mutations. Nat. Methods 7(4), 248-49 (2010). doi:10.1038/nmeth0410-248 CrossRef
  26. R. Calabrese, E. Capriotti, P. Fariselli, P.L. Martelli, R. Casadio, Functional annotations improve the predictive score of human disease-related mutations in proteins. Hum. Mutat. 30(8), 1237-244 (2009). doi:10.1002/humu.21047 7">CrossRef
  27. I.B. Rogozin, L. Milanesi, Analysis of donor splice sites in different eukaryotic organisms. J. Mol. Evol. 45(1), 50-9 (1997) 7/PL00006200">CrossRef
  28. R.I. Dogan, SplicePort http://spliceport.cs.umd.edu/ (2011). Accessed 01 Dec 2011
  29. S.M. Hebsgaard, P.G. Korning, N. Tolstrup, J. Engelbrecht, P. Rouze, S. Brunak, Splice site prediction in Arabidopsis thaliana pre-mRNA by combining local and global sequence information. Nucleic Acids Res. 24(17), 3439-452 (1996) 7.3439">CrossRef
  30. GeneSplicer Web Interface. http://www.cbcb.umd.edu/software/GeneSplicer/gene_spl.shtml. Accessed 01 Dec 2011
  31. The International Hap Map Project, Nature 426(6968), 789-96 (2003). doi:10.1038/nature02168 CrossRef
  32. Exome Variant Server, NHLBI exome sequencing project (ESP). http://evs.gs.washington.edu/EVS/. Accessed 26/10/2011 2011
  33. L. Shen, J. Glowacki, S. Zhou, Inhibition of adipocytogenesis by canonical WNT signaling in human mesenchymal stem cells. Exp. Cell Res. 317(13), 1796-803 (2011). doi:10.1016/j.yexcr.2011.05.018 CrossRef
  34. A map of human genome variation from population-scale sequencing. Nature 467(7319), 1061-073. doi: 10.1038/nature09534
  35. S.A. Ugur, A. Tolun, Homozygous WNT10b mutation and complex inheritance in split-hand/foot malformation. Hum. Mol. Genet. 17(17), 2644-653 (2008). doi:10.1093/hmg/ddn164 CrossRef
  36. A. Blattner, A.R. Huber, B. Rothlisberger, Homozygous nonsense mutation in WNT10B and sporadic split-hand/foot malformation (SHFM) with autosomal recessive inheritance. Am J Med Genet A 152A(8), 2053-056 (2010). doi:10.1002/ajmg.a.33504 CrossRef
  37. S. Khan, S. Basit, F. Zimri, N. Ali, G. Ali, M. Ansar, W. Ahmad, A novel homozygous missense mutation in WNT10B in familial split-hand/foot malformation. Clin. Genet. (2011). doi:10.1111/j.1399-0004.2011.01698.x
  
• 作者单位：Jasmijn K. Van Camp (1)
  Doreen Zegers (1)
  Stijn L. Verhulst (2)
  Kim Van Hoorenbeeck (2)
  Guy Massa (3)
  An Verrijken (4)
  Kristine N. Desager (2)
  Luc F. Van Gaal (4)
  Wim Van Hul (1)
  Sigri Beckers (1)
  
  1. Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium
  2. Department of Paediatrics, Antwerp University Hospital, Wilrijkstraat 10, 2650, Antwerp, Belgium
  3. Department of Paediatrics, Jessa Hospital, Stadsomvaart 11, 3500, Hasselt, Belgium
  4. Department of Endocrinology, Diabetology and Metabolic Diseases, Antwerp University Hospital, Wilrijkstraat 10, 2650, Antwerp, Belgium
  

文摘

Wingless-type MMTV integration site family, member 10B (WNT10B) is an activator of the Wnt pathway. The Wnt pathway is known to play an important role in maintenance and differentiation of stem cells and has been implicated in the origination of obesity. To evaluate the role of genetic variation in WNT10B in obesity further, we performed a mutation analysis on Belgian obese patients and control subjects. A mutation analysis of WNT10B by means of high-resolution melting curve analysis and direct sequencing was performed on 546 obese children and adolescents (mean Z-score of 2.6?±?0.6 and 2.5?±?0.4 respectively), 86 morbidly obese adults (mean BMI of 48.0?±?0.4?kg/m2) and 447 lean, healthy controls (mean BMI of 22.1?±?1.7?kg/m2). A total of five novel non-synonymous variants were identified. R228Q was the only coding, non-synonymous variant that was exclusively found in patients, but the variant did not co-segregate with obesity in the three investigated siblings. The remaining four variants were either found both in cases and in control samples (G181D) or only in control samples (A108P, S187R and P315S). The frequency of non-synonymous variants in lean individuals (0.9?%) was higher than in obese individuals (0.3?%) and familial co-segregation of the most promising variant in patients could not be demonstrated. Therefore, we conclude that variations in WNT10B do not contribute to human monogenic obesity in our population.