PMID- 10486325
OWN - NLM
STAT- MEDLINE
DCOM- 20001002
LR  - 20181113
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 65
IP  - 4
DP  - 1999 Oct
TI  - Genome scan for predisposing loci for distal interphalangeal joint
      osteoarthritis: evidence for a locus on 2q.
PG  - 1060-7
AB  - 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.
FAU - Leppavuori, J
AU  - Leppavuori J
AD  - Department of Human Molecular Genetics, National Public Health Institute,
      University of Helsinki, Finland.
FAU - Kujala, U
AU  - Kujala U
FAU - Kinnunen, J
AU  - Kinnunen J
FAU - Kaprio, J
AU  - Kaprio J
FAU - Nissila, M
AU  - Nissila M
FAU - Heliovaara, M
AU  - Heliovaara M
FAU - Klinger, N
AU  - Klinger N
FAU - Partanen, J
AU  - Partanen J
FAU - Terwilliger, J D
AU  - Terwilliger JD
FAU - Peltonen, L
AU  - Peltonen L
LA  - eng
SI  - OMIM/147760
SI  - OMIM/147810
SI  - OMIM/165720
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Genetic Markers)
SB  - IM
MH  - Adult
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 2/*genetics
MH  - Chromosomes, Human, Pair 4/genetics
MH  - Chromosomes, Human, Pair 7/genetics
MH  - Female
MH  - Finger Joint/metabolism/*pathology
MH  - Finland
MH  - Genes, Dominant/genetics
MH  - Genes, Recessive/genetics
MH  - Genetic Linkage/*genetics
MH  - Genetic Markers/genetics
MH  - Genome, Human
MH  - Haplotypes/genetics
MH  - Humans
MH  - Male
MH  - Matched-Pair Analysis
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Nuclear Family
MH  - Osteoarthritis/*genetics/pathology
MH  - Statistics, Nonparametric
PMC - PMC1288239
EDAT- 1999/09/16 09:00
MHDA- 2000/10/07 11:01
CRDT- 1999/09/16 09:00
PHST- 1999/09/16 09:00 [pubmed]
PHST- 2000/10/07 11:01 [medline]
PHST- 1999/09/16 09:00 [entrez]
AID - S0002-9297(07)62609-3 [pii]
AID - 10.1086/302569 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Oct;65(4):1060-7. doi: 10.1086/302569.