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PMID: 10486325 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Genome scan for predisposing loci for distal interphalangeal joint osteoarthritis: evidence for a locus on 2q.

American journal of human genetics ·Vol. 65 ·No. 4 ·1999-10-00 ·Pages 1060-7

Leppävuori J, Kujala U, Kinnunen J, Kaprio J, Nissilä M, Heliövaara M, Klinger N, Partanen J, Terwilliger JD, Peltonen L

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.

MeSH Terms
Adult Chromosome Mapping Chromosomes, Human, Pair 2/genetics Chromosomes, Human, Pair 4/genetics Chromosomes, Human, Pair 7/genetics Female Finger Joint/metabolism,pathology Finland Genes, Dominant/genetics Genes, Recessive/genetics Genetic Linkage/genetics Genetic Markers/genetics Genome, Human Haplotypes/genetics Humans Male Matched-Pair Analysis Middle Aged Molecular Sequence Data Nuclear Family Osteoarthritis/genetics,pathology Statistics, Nonparametric
Chemicals
Genetic Markers
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Leppävuori J
Department of Human Molecular Genetics, National Public Health Institute, University of Helsinki, Finland.
Kujala U
Kinnunen J
Kaprio J
Nissilä M
Heliövaara M
Klinger N
Partanen J
Terwilliger J D
Peltonen L
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
DOI
10.1086/302569
Published
1999-10-00
Pages
1060-7
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1288239
Subset
IM
Databases
OMIM
147760, 147810, 165720
External Links
PubMed source DOI: 10.1086/302569 PMC Full Text View journal details
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