TY - JOUR
T1 - Variation in femoral length is associated with polymorphisms in RUNX2 gene
AU - Ermakov, Sergey
AU - Malkin, Ida
AU - Kobyliansky, Eugene
AU - Livshits, Gregory
N1 - Funding Information:
The study was performed in partial fulfillment of the doctoral degree requirements of Sergey Ermakov. This study was supported by Israel National Science Foundation (Grant No. 1042/04). We thank Dr. Svetlana Trofimov (Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University) for help in DNA preparation, Dr. Mira Korner and her staff (The Center for Genomic Technologies, The Institute of Life Sciences, The Hebrew University of Jerusalem) for genotyping of the samples and Galit Schwartz (Applied Biosystems, Agentek-Israel) for her assistance. Constructive and positive comments of the anonymous reviewers are also greatly appreciated.
PY - 2006/2
Y1 - 2006/2
N2 - Introduction: Bone size is an important determinant of bone strength. Although it is well established that bone size traits are under the strong genetic control, genes involved in their determination are poorly characterized. The major objective of the present study was to test hypothesis of possible association between three RUNX2 SNP polymorphisms (rs2819858, rs1406846, rs2819854) and anthropometrical femoral length (FEML). In addition, the possibility of association between anthropometrical tibial length (TIBL) and stature and chosen RUNX2 polymorphisms was tested. Materials and methods: The study was conducted on 265 nuclear families comprised of a total of 904 individuals. DNA samples were available for 705 individuals, belonging to 212 nuclear families. Three different transmission disequilibrium tests (TDTs), population-based and pedigree-based (PDT) association analyses were implemented in order to test the working hypothesis. Results: The results unambiguously and consistently demonstrated significant association for FEML regardless of the specific polymorphism tested and type of analysis implemented. The P values obtained by TDTs ranged between 0.0155 and 0.0007. The effect of RUNX2 polymorphisms was estimated to explain 1.9% of the total FEML variation after adjustment for sex and age. The data suggested that the strength of association between RUNX2 polymorphisms and FEML may be higher in females (P = 0.007) than in males (P = 0.046), according to PDT. Conversely, no reliable evidence of association between RUNX2 polymorphisms and either TIBL or stature was found. Conclusions: For the first time, the evidence of association between RUNX2 polymorphisms and FEML was provided. The results of the present research contribute to the deeper understanding of the genetic architecture of femoral size and introduce the issues of site and sex dependency of the extent of RUNX2 effect. Further studies are required to confirm our findings, specifically focused on clinically oriented sites of skeleton, like femoral neck.
AB - Introduction: Bone size is an important determinant of bone strength. Although it is well established that bone size traits are under the strong genetic control, genes involved in their determination are poorly characterized. The major objective of the present study was to test hypothesis of possible association between three RUNX2 SNP polymorphisms (rs2819858, rs1406846, rs2819854) and anthropometrical femoral length (FEML). In addition, the possibility of association between anthropometrical tibial length (TIBL) and stature and chosen RUNX2 polymorphisms was tested. Materials and methods: The study was conducted on 265 nuclear families comprised of a total of 904 individuals. DNA samples were available for 705 individuals, belonging to 212 nuclear families. Three different transmission disequilibrium tests (TDTs), population-based and pedigree-based (PDT) association analyses were implemented in order to test the working hypothesis. Results: The results unambiguously and consistently demonstrated significant association for FEML regardless of the specific polymorphism tested and type of analysis implemented. The P values obtained by TDTs ranged between 0.0155 and 0.0007. The effect of RUNX2 polymorphisms was estimated to explain 1.9% of the total FEML variation after adjustment for sex and age. The data suggested that the strength of association between RUNX2 polymorphisms and FEML may be higher in females (P = 0.007) than in males (P = 0.046), according to PDT. Conversely, no reliable evidence of association between RUNX2 polymorphisms and either TIBL or stature was found. Conclusions: For the first time, the evidence of association between RUNX2 polymorphisms and FEML was provided. The results of the present research contribute to the deeper understanding of the genetic architecture of femoral size and introduce the issues of site and sex dependency of the extent of RUNX2 effect. Further studies are required to confirm our findings, specifically focused on clinically oriented sites of skeleton, like femoral neck.
KW - Bone size
KW - Femur
KW - SNP
KW - Stature
KW - TDT
UR - http://www.scopus.com/inward/record.url?scp=31544483312&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2005.08.008
DO - 10.1016/j.bone.2005.08.008
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AN - SCOPUS:31544483312
SN - 8756-3282
VL - 38
SP - 199
EP - 205
JO - Bone
JF - Bone
IS - 2
ER -