Family-based association study of ROR2 polymorphisms with an array of radiographic hand bone strength phenotypes.
For the first time the study provides evidence of association of radiographic hand bone length (BL) and bone mineral density (BMD) with polymorphisms in ROR2 gene that plays important role in skeletal development. This contributes to better understanding of bone physiology and may have application in clinical practice.


OBJECTIVE
Bone size and bone mineral density (BMD) are major determinants of bone strength. Identification of genes affecting these traits' variability is important for better understanding of normal and pathological bone physiology and identification of the individuals at risk for bone fracture. This study tested the hypothesis of association of radiographic hand bone length (BL) and BMD with polymorphisms in ROR2 gene that is important in skeletal development.


METHODS
Nineteen ROR2 SNPs were genotyped in 705 individuals, belonging to 212 nuclear families. The four tagging SNPs (tSNPs) and the pairwise haplotypes between adjacent tSNPs were tested for association with series of hand BL and BMD measurements, adjusted for covariates, using family-based association tests.


RESULTS
We observed significant associations with BL and BMD mean values for all 18 studied hand bones (p = 0.0080, 0.0030), mean BL and BMD for proximal phalanges (p = 0.0218, 0.0060) and metacarpal bones (p = 0.0014, 0.0004). In the latter, the association remained significant after correction for multiple testing.


CONCLUSIONS
The region of the first through the second ROR2 introns is most likely to contain the functional polymorphism/s responsible for the observed associations. Further studies are required to identify the ROR2 functional polymorphism/s affecting bone size and BMD variation.
Ermakov
S
S
Human Population Biology Research Unit, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
Malkin
I
I
Keter
M
M
Kobyliansky
E
E
Livshits
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D005838:Genotype; D050276:Hand Bones / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000502:physiology*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011859:Radiography; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D011956:Receptors, Cell Surface / Q000235:genetics*
D005819:Genetic Markers; D011956:Receptors, Cell Surface; C078717:ROR2 protein, human; D057050:Receptor Tyrosine Kinase-like Orphan Receptors