Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins

Macgregor, Alexander; Snieder, Harold; Rigby, Alan S.; Koskenvuo, Markku; Kaprio, Jaakko; Aho, Kimmo; Silman, Alan J.

doi:10.1002/1529-0131(200001)43:1<30::aid-anr5>3.0.co;2-b

Cited by 965 publications

(520 citation statements)

References 21 publications

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“…The fraction of CD4 þ CD28 À T lymphocytes is increased in RA vasculitis in comparison with other clinical forms of RA. 14,16,17 Both T and NK cells are involved in RA pathology, [1][2][3][4] but their contribution to different manifestations of the disease is largely unknown. Moreover, the mechanisms of KIR inhibitory and activatory functions in T cells are different from those in NK cells.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 There is a tendency for RA to run in families, and the genetic contribution to disease susceptibility has been estimated at around 60%. 3 One important genetic factor is so-called 'shared epitope' present on several allomorphs of the human leukocyte antigen (HLA) class II, HLA-DR. However, RA is a multifactorial disease, and several other genes are implicated in susceptibility to this condition.…”

Section: Introductionmentioning

confidence: 99%

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Associations of killer cell immunoglobulin-like receptor genes with complications of rheumatoid arthritis

et al. 2007

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We investigated whether killer cell immunoglobulin-like receptor (KIR) genes are risk factor(s) for rheumatoid arthritis (RA) and its clinical manifestations. One hundred and seventy-seven RA patients and 243 healthy individuals were tested for the presence of 11 KIR genes using PCR-SSP method. The frequencies of KIRs in patients with RA were similar to the frequencies in controls. However, RA patients positive for KIR2DL3 and negative for KIR2DS3 had earlier disease diagnosis. Additionally, KIR2DL2 and KIR2DS2 were significantly more frequent among RA patients with extra-articular manifestations and in its subgroup with vasculitis than in controls and in patients without these complications. Furthermore, the frequencies of KIR2DS1 and KIR3DS1 were lower in patients without bone erosions compared with healthy individuals. Relationships between the presence or absence of autoantibodies (rheumatoid factor and anti-cyclic citrullinated peptide) and KIR frequencies were also evaluated, but no significant differences were observed. These results suggest that particular clinical manifestations of RA may have different genetic backgrounds with respect to KIR genotype.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Associations of killer cell immunoglobulin-like receptor genes with complications of rheumatoid arthritis

et al. 2007

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“…In the proximity of the centromeric regions, this mapping approach is inaccurate because the centromeric regions have suppressed recombination. Therefore, we reperformed analysis setting the recombination to zero for the six chromosomes with large centromeres (1,3,9,11,16,19). Excluding recombination in these regions led to slightly lower LOD scores (further results available upon request).…”

Section: Study Populationmentioning

confidence: 99%

“…2 Twin analysis, for example, estimated the heritability of RA to be about 60%. 3 The strength of the genetic component has also been estimated by computing the relative recurrence risk for siblings (l s ) of RA probands compared with that for the general population. 4 Due to uncertainty about the prevalence of RA in Caucasian populations, as well as variability in the phenotype, the estimated increase in risk to siblings varies between 5 and 10.…”

Section: Introductionmentioning

confidence: 99%

High-density SNP analysis of 642 Caucasian families with rheumatoid arthritis identifies two new linkage regions on 11p12 and 2q33

et al. 2006

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We have completed a genome wide linkage scan using 45700 informative single-nucleotide polymorphism (SNP) markers (Illumina IV SNP linkage panel) in 642 Caucasian families containing affected sibling pairs with rheumatoid arthritis (RA), ascertained by the North American Rheumatoid Arthritis Consortium. The results show striking new evidence of linkage at chromosomes 2q33 and 11p12 with logarithm of odds (LOD) scores of 3.52 and 3.09, respectively. In addition to a strong and broad linkage interval surrounding the major histocompatibility complex (LOD416), regions with LOD42.5 were observed on chromosomes 5 and 10. Additional linkage evidence (LOD scores between 1.46 and 2.35) was also observed on chromosomes 4, 7, 12, 16 and 18. This new evidence for multiple regions of genetic linkage is partly explained by the significantly increased information content of the Illumina IV SNP linkage panel (75.6%) compared with a standard microsatellite linkage panel utilized previously (mean 52.6%). Stratified analyses according to whether or not the sibling pair members showed elevated anticyclic citrullinated peptide titers indicates significant variation in evidence for linkage among strata on chromosomes 4, 5, 6 and 7. Overall, these new linkage data should reinvigorate efforts to utilize positional information to identify susceptibility genes for RA.

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“…Several genetic studies of families, twins, and siblings showing familial aggregation and twin and sibling concordance have demonstrated a clear genetic component of arthritis (2,3). Inheritance of RA has been shown to depend upon the major histocompatibility complex (MHC) haplotype as well as other, hitherto-unidentified genes with varying influences (4,5). A recently published linkage analysis of human RA estimated the heritable component of RA to be as high as 60% (5).…”

mentioning

confidence: 99%

A comparative genetic analysis between collagen‐induced arthritis and pristane‐induced arthritis

Olofsson¹,

Lu²,

Holmberg³

et al. 2003

Arthritis & Rheumatism

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Objective. To compare the genetic regulation of collagen-induced arthritis (CIA) with that of pristaneinduced arthritis (PIA) in rats.Methods. A genome-wide linkage analysis of an (E3 ؋ DA)DA backcross of rats with CIA (n ‫؍‬ 364 male rats; the same strain combinations as previously used to determine the genetic control of PIA) was performed. The strongest loci in both CIA and PIA (i.e., Cia12/Pia4 and Cia13/Pia7) were isolated in congenic strains. Susceptibility in both congenic strains was tested in rats with CIA and in rats with PIA.Results. We found a striking, although not complete, similarity of the arthritis-controlling loci in CIA and in PIA, as well as the previously defined loci associated with cartilage destruction, antibody production, and the acute-phase response. All major PIA quantitative trait loci (QTLs) identified in early severe arthritis were also strong regulators of CIA. The 2 strongest QTLs, Cia12/Pia4 on chromosome 12 and Cia13/Pia7 on chromosome 4, were also analyzed in congenic strains with DA or E3 as the background genome. Consistent with the results of linkage analysis, the congenic strain experiments showed that the chromosome 4 locus was more penetrant in CIA than in PIA, while the chromosome 12 locus almost completely dominated the control of PIA severity.Conclusion. The underlying genetic control of CIA was found to have many, but not all, pathogenic mechanisms in common with PIA, despite the use of a cartilage-specific antigen (type II collagen) to induce CIA but not PIA.

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Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins

Cited by 965 publications

References 21 publications

Associations of killer cell immunoglobulin-like receptor genes with complications of rheumatoid arthritis

Associations of killer cell immunoglobulin-like receptor genes with complications of rheumatoid arthritis

High-density SNP analysis of 642 Caucasian families with rheumatoid arthritis identifies two new linkage regions on 11p12 and 2q33

A comparative genetic analysis between collagen‐induced arthritis and pristane‐induced arthritis

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