title: Association of ANKH gene polymorphisms with radiographic hand bone size and geometry in a Chuvasha population.
abstract: We performed a family-based association study to test the hypothesis that genetic variation at the human orthologue of the mouse progressive ankylosis gene (ANKH) is involved in determining bone size (BS) and bone geometry (BG). The study population comprised 126 nuclear families with 574 adult Chuvashian individuals living in small villages in the Russian Federation. Quantitative bone traits were determined by analyzing plain hand radiographs. Familial correlations for all studied traits revealed a high degree of heritability in this ethnically homogeneous population. Three simple tandem repeat (STR) polymorphisms, one intragenic and two flanking markers, as well as six single nucleotide polymorphisms (SNPs) were tested. The SNPs were detected by re-sequencing experiments and covered ANKH exons with their flanking splice sites and the promoter region. We used three different transmission disequilibrium tests (TDTs) and obtained multiple significant association signals for all investigated bone traits. Alleles of several markers located at different positions of the ANKH locus, including the promoter, consistently revealed the association. The bone traits tested are closely related to bone fragility suggesting a role for ANKH in osteoporosis.
authors.affiliation: Department of Anatomy and Anthropology, Human Population Biology Research Unit, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ida
authors.initials: I
authors.lastname: Malkin
authors.forename: Stefan
authors.initials: S
authors.lastname: Dahm
authors.forename: Anita
authors.initials: A
authors.lastname: Suk
authors.forename: Eugene
authors.initials: E
authors.lastname: Kobyliansky
authors.forename: Mohammad
authors.initials: M
authors.lastname: Toliat
authors.forename: Nico
authors.initials: N
authors.lastname: Ruf
authors.forename: Gregory
authors.initials: G
authors.lastname: Livshits
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002348:Carpal Bones / Q000000981:diagnostic imaging* / Q000502:physiology*; D005260:Female; D050723:Fractures, Bone / Q000235:genetics / Q000503:physiopathology; D005787:Gene Frequency / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics*; D006225:Hand / Q000000981:diagnostic imaging / Q000502:physiology; D006801:Humans; D016014:Linear Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D028061:Phosphate Transport Proteins; D011110:Polymorphism, Genetic / Q000235:genetics*; D011859:Radiography; D012426:Russia
chemical_list: C498770:ANKH protein, human; D008565:Membrane Proteins; D028061:Phosphate Transport Proteins