Group MäkitieGenetic Determinants of Osteoporosis
Our group aims to identify new genes involved in the development of osteoporosis and to study the role of previously characterized genes and their variation in osteoporosis. By learning more about the genetic causes it is possible to develop new tools for effective screening and early treatment.
We have identified several large families with inherited, childhood-onset osteoporosis, presenting with multiple peripheral and spinal compression factures by early adulthood. In many of the families we have identified the disease-causing mutations. We have described a heterozygous missense mutation in WNT1 that leads to aberrant WNT-signaling and causes an abnormal skeletal phenotype in children and young adults, and a new X-linked PLS3-mutation, causing severe osteoporosis in men. By exome and whole-genome sequencing studies we have recently identified three new genes associated with early-onset osteoporosis and studies are ongoing in several other families with unidentified genetic causes.
We have also studied LRP5, a gene encoding a co-receptor for WNT-ligands, and characterized several of its novel mutations in recessive OPPG-syndrome, primary osteoporosis and low bone mineral density in young men and children. Further, we have studied the role of LRP6, FGF23, WNT16, XYLT2 and several other genes in early-onset osteoporosis and have investigated the effect of genetic variation on bone mineral density and mineral homeostasis in children and adolescents. In addition, we have studied bone characteristics and gene copy number variations in severe early-onset obesity, and new family studies on this topic are ongoing.
Minna Pekkinen, PhD, Administrative Group Leader
Saila Laakso, MD PhD
Pauliina Utriainen, MD PhD
Maria Enlund-Cerullo, MD
Mehran Kausar, MSc
Svetlana Kostjukovitch, MD
Petra Loid, MD
Riikka Mäkitie, MD
Ilkka Vuorimies, MD
Mira Aronen, Biomedical Laboratory Scientist
Rhea Paajanen, Research Nurse
Päivi Turunen, Research Nurse
Laine CM, Joeng KS, Campeau PM, Kiviranta R, Tarkkonen K, Grover M, Lu JT, Pekkinen M, Wessman M, Heino TJ, Nieminen-Pihala V, Aronen M, Laine T, Kröger H, Cole WG, Lehesjoki AE, Nevarez L, Krakow D, Curry CJ, Cohn DH, Gibbs RA, Lee BH, Mäkitie O. WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta. N Engl J Med. 2013 May 9;368(19):1809-16. doi: 10.1056/NEJMoa1215458.
Laine CM, Wessman M, Toiviainen-Salo S, Kaunisto MA, Mäyränpää MK, Laine T, Pekkinen M, Kröger H, Välimäki VV, Välimäki MJ, Lehesjoki AE, Mäkitie O (2015) A novel splice mutation in PLS3 causes X-linked early onset low-turnover osteoporosis. J Bone Miner Res. 2015 Mar;30(3):510-8. doi: 10.1002/jbmr.2355.
Mäkitie RE, Haanpää M, Valta H, Pekkinen M, Laine CM, Lehesjoki AE, Schalin-Jäntti C, Mäkitie O. (2016) Skeletal Characteristics of WNT1 Osteoporosis in Children and Young Adults. J Bone Miner Res. 2016 Mar 23. doi: 10.1002/jbmr.2841
Kämpe AJ, Mäkitie RE, Mäkitie O. New Genetic Forms of Childhood-Onset Primary Osteoporosis. Horm Res Paediatr. 2015;84(6):361-9. doi: 10.1159/000439566.
Taylan F, Costantini A, Coles N, Pekkinen M, Héon E, Şıklar Z, Berberoğlu M, Kämpe A, Kıykım E, Grigelioniene G, Tüysüz B, Mäkitie O. (2016) Spondyloocular Syndrome: Novel Mutations in XYLT2 Gene and Expansion of the Phenotypic Spectrum. J Bone Miner Res. 2016 Aug;31(8):1577-85. doi: 10.1002/jbmr.2834.
Mäyränpää, M. K., Viljakainen, H. T., Toiviainen-Salo, S-M., Kallio, P. E. & Makitie, O. (2012) Impaired bone health and asymptomatic vertebral compressions in fracture-prone children: a case-control study. 2012 In : J Bone Miner Res. 2012: 27, 6, p. 1413-1424 12 p.
Saarinen, A-R.,Mäyränpää, M. K.Lehesjoki, A-E. & Mäkitie, O. (2010) Low-density lipoprotein receptor-related protein 5 (LRP5) variation in fracture prone children.In : Bone. 46, 4, p. 940-945 6 p.
Laine CM, Chung BD, Susic M, Prescott T, Semler O, Fiskerstrand T, D'Eufemia P, Castori M, Pekkinen M, Sochett E, Cole WG, Netzer C, Mäkitie O. Novel mutations affecting LRP5 splicing in patients with osteoporosis-pseudoglioma syndrome (OPPG). Eur J Hum Genet. 2011 Aug;19(8):875-81. doi: 10.1038/ejhg.2011.42.
Pekkinen M, Laine CM, Mäkitie R, Leinonen E, Lamberg-Allardt C, Viljakainen H, Mäkitie O. FGF23 gene variation and its association with phosphate homeostasis and bone mineral density in Finnish children and adolescents. Bone. 2015 Feb;71:124-30. doi: 10.1016/j.bone.2014.10.013. Epub 2014 Oct 24.
Viljakainen H, Andersson-Assarsson JC, Armenio M, Pekkinen M, Pettersson M, Valta H, Lipsanen-Nyman M, Mäkitie O, Lindstrand A. Low Copy Number of the AMY1 Locus Is Associated with Early-Onset Female Obesity in Finland. PLoS One. 2015 Jul 1;10(7):e0131883. doi: 10.1371/journal.pone.0131883.
Folkhälsan Research Foundation
Academy of Finland
EVO Governmental Grants
Foundation for Pediatric Research
Novo Nordisk Foundation
Sigrid Jusélius Foundation
Prof. Juha Kere, Prof. Anna-Elina Lehesjoki, Folkhälsan
Prof. Matti Välimäki, Doc. Camilla Schalin-Jäntti, Dr. Panu Kovanen, Dr. Helena Valta, Helsinki University Hospital
Doc. Riku Kiviranta, University of Turku
Dr. Tuukka Niinimäki, Dr. Riitta Niinimäki, Dr. Sakari Kakko, Prof. Miika Nieminen, Dr. Jaakko Niinimäki, Oulu University Hospital
Prof. Heikki Kröger, Kuopio University Hospital
Prof. Christel Lamberg-Allardt, University of Helsinki
Doc. Anna Lindstrand, Karolinska Institute, Stockholm, Sweden
Prof. Harald Jüppner, Massachusetts General Hospital, Boston, USA
Prof. Zeunep Siklar, University of Ankara, Turkey
Prof. Beyhan Tuysuz, University of Istanbul, Turkey
Dr. Fernando Rivadeneira, Erasmus University Rotterdam, Netherlands
Prof. Olle Kämpe, Karolinska Institutet, Sweden
Prof. Renata Pereira University of California, Los Angeles, USA