Dataset Information

Specific association of type 1 diabetes mellitus with anti-cyclic citrullinated peptide-positive rheumatoid arthritis.

ABSTRACT: The co-occurrence of autoimmune diseases such as rheumatoid arthritis (RA) and type 1 diabetes mellitus (DM) has been reported in individuals and families. In this study, the strength and nature of this association were investigated at the population level in a Swedish case-control cohort.For this case-control study, 1,419 patients with incident RA diagnosed between 1996 and 2003 were recruited from university, public, and private rheumatology units throughout Sweden; 1,674 matched control subjects were recruited from the Swedish national population registry. Sera from the subjects were tested for the presence of antibodies to cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), and the 620W PTPN22 allele. Information on a history of diabetes was obtained by questionnaire, telephone interview, and/or medical record review. The prevalence of type 1 DM and type 2 DM was compared between patients with incident RA and control subjects and further stratified for the presence of anti-CCP, RF, and the PTPN22 risk allele.Type 1 DM was associated with an increased risk of RA (odds ratio [OR] 4.9, 95% confidence interval [95% CI] 1.8-13.1), and this association was specific for anti-CCP-positive RA (OR 7.3, 95% CI 2.7-20.0), but not anti-CCP-negative RA. Further adjustment for the presence of PTPN22 attenuated the risk of anti-CCP-positive RA in patients with type 1 DM to an OR of 5.3 (95% CI 1.5-18.7). No association between RA and type 2 DM was observed.The association between type 1 DM and RA is specific for a particular RA subset, anti-CCP-positive RA. The risk of developing RA later in life in patients with type 1 DM may be attributed, in part, to the presence of the 620W PTPN22 allele, suggesting that this risk factor may represent a common pathway for the pathogenesis of these 2 diseases.

SUBMITTER: Liao KP

PROVIDER: S-EPMC2768389 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Specific association of type 1 diabetes mellitus with anti-cyclic citrullinated peptide-positive rheumatoid arthritis.

Liao Katherine P KP Gunnarsson Marie M Källberg Henrik H Ding Bo B Plenge Robert M RM Padyukov Leonid L Karlson Elizabeth W EW Klareskog Lars L Askling Johan J Alfredsson Lars L

Arthritis and rheumatism 20090301 3

<h4>Objective</h4>The co-occurrence of autoimmune diseases such as rheumatoid arthritis (RA) and type 1 diabetes mellitus (DM) has been reported in individuals and families. In this study, the strength and nature of this association were investigated at the population level in a Swedish case-control cohort.<h4>Methods</h4>For this case-control study, 1,419 patients with incident RA diagnosed between 1996 and 2003 were recruited from university, public, and private rheumatology units throughout S ...[more]

PMID: 19248096

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Project description:The PTPN22 1858C/T polymorphism has been associated with several autoimmune diseases including rheumatoid arthritis (RA). We have shown that carriage of the T variant (CT or TT) of PTPN22 in combination with anti-cyclic citrullinated peptide (anti-CCP) antibodies highly increases the odds ratio for developing RA. In the present study we analysed the association between the PTPN22 1858C/T polymorphism and early RA in patients from northern Sweden, related the polymorphism to autoantibodies and the HLA-DR shared epitope, and analysed their association with markers for disease activity and progression. The inception cohort includes individuals who also donated samples before disease onset. A case-control study was performed in patients (n = 505; 342 females and 163 males) with early RA (mean duration of symptoms = 6.3 months) and in population-based matched controls (n = 970) from northern Sweden. Genotyping of the PTPN22 1858C/T polymorphism was performed using a TaqMan instrument. HLA-shared epitope alleles were identified using PCR sequence-specific primers. Anti-CCP2 antibodies were determined using enzyme-linked immunoassays. Disease activity (that is, the number of swollen and tender joints, the global visual analogue scale, and the erythrocyte sedimentation rate) was followed on a regular basis (that is, at baseline and after 6, 12, 18 and 24 months). Both the 1858T allele and the carriage of T were associated with RA (chi2 = 23.84, P = 0.000001, odds ratio = 1.69, 95% confidence interval = 1.36-2.11; and chi2 = 22.68, P = 0.000002, odds ratio = 1.79, 95% confidence interval = 1.40-2.29, respectively). Association of the 1858T variant with RA was confined to seropositive disease. Carriage of 1858T and the presence of anti-CCP antibodies was independently associated with disease onset at an earlier age (P < 0.05 and P < 0.01, respectively), while the combination of both resulted in an even earlier age at onset. Smoking was identified as a risk factor independent of the 1858T variant and anti-CCP antibodies.

Project description:OBJECTIVE:To evaluate the incidence of cardiovascular disease (CVD) morbidity and mortality over the course of 10 years among the more than 160,000 postmenopausal women in the Women's Health Initiative (WHI) in relation to self-reported rheumatoid arthritis (RA), taking disease-modifying antirheumatic drugs (DMARDs), anti-cyclic citrullinated peptide (anti-CCP) positivity, rheumatoid factor (RF) positivity, CVD risk factors, joint pain, and inflammation (white blood cell count and interleukin-6 levels). METHODS:Anti-CCP and RF were measured in a sample of WHI participants with self-reported RA (n?=?9,988). RA was classified as self-reported RA plus anti-CCP positivity and/or taking DMARDs. Anti-CCP-negative women with self-reported RA and not taking DMARDs were classified as having "unverified RA." RESULTS:Age-adjusted rates of coronary heart disease (CHD), stroke, CVD, fatal CVD, and total mortality were higher in women with RA than in women with no reported RA, with multivariable-adjusted hazard ratios of 1.46 (95% confidence interval [95% CI] 1.17-1.83) for CHD and 2.55 (95% CI 1.86-3.51) for fatal CVD. Among women with RA, anti-CCP positivity and RF positivity were not significantly associated with higher risk of any outcomes, despite slightly higher risk of death for those who were anti-CCP positive than for those who were anti-CCP negative. Joint pain severity and CVD risk factors were strongly associated with CVD risk, even in women with no reported RA. CVD incidence was increased in women with RA versus women with no reported RA at almost all risk factor levels, except for low levels of joint pain or inflammation. Among women with RA, inflammation was more strongly associated with fatal CVD and total mortality than with CHD or CVD. CONCLUSION:Among postmenopausal women, RA was associated with 1.5-2.5-fold higher CVD risk. CVD risk was strongly associated with CVD risk factors, joint pain severity, and inflammation, but not with anti-CCP positivity or RF positivity.

Dataset Information

Specific association of type 1 diabetes mellitus with anti-cyclic citrullinated peptide-positive rheumatoid arthritis.

Publications

Specific association of type 1 diabetes mellitus with anti-cyclic citrullinated peptide-positive rheumatoid arthritis.

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