Immunogenetic differencies between patients with familial and non-familial rheumatoid arthritis

Laivoranta-Nyman, S; Möttönen, Timo; Luukkainen, R; Hakala, M; Yli-Kerttula, U; Hannonen, Pekka; Tuokko, Juha; Toivanen, Auli; Ilonen, Jorma

doi:10.1136/ard.59.3.173

Cited by 15 publications

(5 citation statements)

References 38 publications

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“…The numbers are still small and the p value for the difference in DRB1*13 is significant only when calculated without correction for the number of comparisons made. However, we detected a protective effect of HLA-DRB1*13 in RA in both familial and sporadic cases,10and this has also been found in several earlier studies, though not always reaching a statistical significance 12-14. The effect might also be due to the associated DQ alleles, which have been suggested to be of primary importance in genetic protection against the disease 15…”

Section: Discussionsupporting

confidence: 88%

Differences between female and male patients with familial rheumatoid arthritis

Laivoranta-Nyman

2001

Annals of the Rheumatic Diseases

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Objective-To determine whether there are genetic diVerences between female and male patients with familial rheumatoid arthritis (RA). Methods-45 men and 119 women from 78 families with RA who all had at least one first degree relative with RA were compared. HLA-DRB1 alleles were analysed, including DRB1*04 subtypes and associations of DRB1*04 haplotypes with DQB1*0301 or DQB1*0302 alleles, the age of the patients at disease onset, the presence of rheumatoid factor (RF), joint erosions, and rheumatoid nodules. Results-HLA-DRB1*13 allele (the subtype allele of DR6, reported to be protective against the development of RA) was found in 14/119 (12%) of female but in none of the male patients (p=0.036). The HLA-DR4 allele was found slightly more often in men than women patients with familial RA (31/45 (69%) v 75/119 (63%), NS). Men were also more often RF positive than women (44/45 (98%) v 98/117 (84%); p=0.031). On the other hand, the mean age at onset of RA was significantly lower in the female group (40.4 years) than in men (46.6 years, p=0.0044). Conclusion-The results indicate that there is stronger genetic background in familial male than female patients with RA in the genetic susceptibility defined by the studied HLA antigens. However, the earlier age of onset of the disease in female group and the increased proportion of women with RA indicate that there are additional sex related predisposing factors enhanced in familial cases. (Ann Rheum Dis 2001;60:413-415) The ratio of the prevalence of women to men with rheumatoid arthritis (RA) has been consistently found to be around 3:1, 1 though the probands from multicase families have been reported as often to be men as women. 2The observations that more women than men develop RA implies the presence of major susceptibility factor(s) other than HLA in female patients.3 These might be hormonal or sex related genetic factors. 4 Some studies suggest that the strength of the known HLA-DR4 association of RA is weaker in women than in men, 4-6 but this has not been confirmed in other studies.3 7 A higher proportion of HLA-DR4 antigen in men than in women might be related to the presence of other susceptibility factors in women.

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Section: Discussionsupporting

confidence: 88%

Differences between female and male patients with familial rheumatoid arthritis

Laivoranta-Nyman

2001

Annals of the Rheumatic Diseases

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“…There is a wide range of results on the association between familial RA and radiographic progression. Some studies report a lack of association [17][18][19][20][21][22][23] and others a considerable influence of familial RA on damage progression [24][25][26][27][28][29]. These apparently contradictory results may be explained by differences in the definitions of familial RA and radiographic progression across studies, and in the study designs and statistical methods used ( Table 3).…”

Section: Discussionmentioning

confidence: 85%

Familial disease, the HLA-DRB1 shared epitope and anti-CCP antibodies influence time at appearance of substantial joint damage in rheumatoid arthritis

Rojas-Villarraga

Díaz

Calvo-Páramo

et al. 2009

Journal of Autoimmunity

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“…Differences between familial and nonfamilial RA have been reported previously. Sanders et al found that the frequency of HLA–DR4 was significantly higher in familial RA cases compared with RA probands without familial RA(4), and this finding has recently been replicated by another group(5).…”

Section: Discussionmentioning

confidence: 87%

“…Previous studies have shown this to be the case with the major RA genetic susceptibility locus, HLA. Probands with a family history of RA are more likely to be DR4 positive and have a younger age at disease onset(4, 5). Studying such multicase RA families may facilitate identification of weak genetic effects.…”

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confidence: 99%

Association between rheumatoid arthritis and polymorphism of tumor necrosis factor receptor II, but not tumor necrosis factor receptor I, in Caucasians

Barton

John

Ollier

et al. 2001

Arthritis & Rheumatism

112

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Objective Tumor necrosis factor (TNF) is a powerful mediator of inflammation in rheumatoid arthritis (RA). In vivo, its acute effects are limited by binding to soluble receptors (TNFR), suggesting that TNFR genes could be important candidate risk factors. The present study was undertaken to investigate association of polymorphisms of TNFRI and TNFRII with RA in subjects in the UK. Methods Unrelated Caucasian RA patients (n = 291) and healthy Caucasian controls (n = 143) were genotyped for A/G polymorphism in exon 1 of TNFRI. From this sample, 240 of the patients and 137 controls were also typed for a single‐nucleotide polymorphism (SNP) in exon 6 of the TNFRII gene. In followup studies, DNA samples from UK Caucasian RA patients with a positive family history (n = 149) and UK Caucasian patients with sporadic RA (n = 208) were also typed for the exon 6 TNFRII polymorphism. Results TNFRI polymorphism was not associated with RA (odds ratio [OR] for GG genotype 0.93, 95% confidence interval [95% CI] 0.54–1.60). For TNFRII, in the initial study group, patients with RA were significantly more likely to be positive for both the G allele and GG genotype than were controls (OR for GG genotype 2.55, 95% CI 1.11–5.86). The association appeared to be confined to those with a family history of RA. This finding was replicated in an independent cohort of patients with familial RA. Conclusion The results of this study provide evidence of association between an SNP in the TNFRII gene and RA, the strongest association being observed in patients with a family history. No evidence of association between RA and TNFRI was demonstrated.

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Immunogenetic differencies between patients with familial and non-familial rheumatoid arthritis

Cited by 15 publications

References 38 publications

Differences between female and male patients with familial rheumatoid arthritis

Differences between female and male patients with familial rheumatoid arthritis

Familial disease, the HLA-DRB1 shared epitope and anti-CCP antibodies influence time at appearance of substantial joint damage in rheumatoid arthritis

Association between rheumatoid arthritis and polymorphism of tumor necrosis factor receptor II, but not tumor necrosis factor receptor I, in Caucasians

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