title: Genome scan for predisposing loci for distal interphalangeal joint osteoarthritis: evidence for a locus on 2q.
abstract: The genetic contribution to common forms of osteoarthritis (OA) is well established but poorly understood. We performed a genome scan, using 302 markers for loci predisposing to distal interphalangeal joint (DIP) OA. To minimize genetic heterogeneity in our study sample, we identified siblings with a severe, radiologically defined phenotype from the nationwide registers of Finland. In the initial genome scan, linkage analysis in 27 sibships gave a pairwise LOD score (Z) >1.00 with nine of the screening markers. In the second stage, additional markers and family members were genotyped in these chromosomal regions. On 2q12-q13, IL1R1 resulted in Z=2.34 at recombination fraction (theta) 0, allowing a dominant mode of inheritance. Association analysis of markers D2S2264, IL1R1, D2S373, and D2S1789 jointly provided some evidence for a shared haplotype among the affected individuals (P value of.012). Also, multipoint nonparametric linkage analysis yielded a P value of.0001 near the locus IL1R1 and P=.0007 approximately 20 cM telomeric near marker D2S1399, which, in two-point analysis, gave Z=1.48 (straight theta=. 02). This chromosomal region on 2q harbors the interleukin 1 gene cluster and, thus, represents a good candidate region for inflammatory and autoimmune disorders. Three additional chromosomal regions-4q26-q27, 7p15-p21, and Xcen-also provided some evidence for linkage, and further analyses would be justified to clarify their potential involvement in the genetic predisposition to DIP OA.
authors.affiliation: Department of Human Molecular Genetics, National Public Health Institute, University of Helsinki, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Leppävuori
authors.forename: U
authors.initials: U
authors.lastname: Kujala
authors.forename: J
authors.initials: J
authors.lastname: Kinnunen
authors.forename: J
authors.initials: J
authors.lastname: Kaprio
authors.forename: M
authors.initials: M
authors.lastname: Nissilä
authors.forename: M
authors.initials: M
authors.lastname: Heliövaara
authors.forename: N
authors.initials: N
authors.lastname: Klinger
authors.forename: J
authors.initials: J
authors.lastname: Partanen
authors.forename: J D
authors.initials: JD
authors.lastname: Terwilliger
authors.forename: L
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D000328:Adult; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D005260:Female; D005384:Finger Joint / Q000378:metabolism / Q000473:pathology*; D005387:Finland; D005799:Genes, Dominant / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D015894:Genome, Human; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D008969:Molecular Sequence Data; D009679:Nuclear Family; D010003:Osteoarthritis / Q000235:genetics* / Q000473:pathology; D018709:Statistics, Nonparametric
chemical_list: D005819:Genetic Markers