| 1. |
- Kristjánsdóttir, Helga, 1966-, et al.
(författare)
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Association of three systemic lupus erythematosus susceptibility factors, PD-1.3A, C4AQ0, and low levels of mannan-binding lectin, with autoimmune manifestations in Icelandic multicase systemic lupus erythematosus families
- 2008
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 58:12, s. 3865-3872
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study autoimmune diseases and autoantibodies in Icelandic multicase systemic lupus erythematosus (SLE) families and to determine the association of 3 SLE susceptibility factors, PD-1.3A, C4AQ0, and low levels of mannan-binding lectin (MBL), with autoimmune disease in this population. Methods: Eight SLE multicase families were studied, comprising a total of 124 family members (23 patients with SLE and 101 relatives). The diagnosis of an autoimmune disease was established and autoantibodies were measured in each family. In addition, PD-1.3A alleles were genotyped, and C4AQ0 allotypes were established by electrophoresis and haplotype analysis. Low levels of MBL were determined using enzyme-linked immunosorbent assay and variant-allele genotyping. Results: In the SLE multicase families there was a high frequency of other autoimmune diseases (32.2%) and a high frequency of autoantibodies (53.2%). Of all family members, 59.7% were determined to have SLE, other autoimmune diseases, antinuclear antibodies, and/or other autoantibodies. The families showed genetic heterogeneity for PD-1.3A, C4AQ0, and low MBL levels; the frequency of each factor ranged from 0% to 85%. The frequencies of PD-1.3A and C4AQ0 were significantly increased in patients with SLE, relatives with other autoimmune diseases, and non-autoimmune disease relatives compared with controls. In the 7 families whose members had low levels of MBL, this factor was significantly associated with SLE, but the frequency of low MBL was decreased in relatives with other autoimmune diseases as compared with non-autoimmune disease relatives and controls. There were indications of an additive effect, and 91% of patients with SLE, 78% of relatives with other autoimmune diseases, and 75% of non-autoimmune disease relatives carried at least 1 of the 3 factors. Conclusion: These results demonstrate a high frequency of autoimmune diseases and autoantibodies in SLE multicase families. PD-1.3A and C4AQ0 are part of a predisposing genetic background. Other genetic and/or environmental factors are necessary for disease expression, demonstrated by a high frequency of PD-1.3A and C4AQ0 in non-autoimmune disease relatives. Low MBL levels may be one such contributing factor. The results of this study provide an example of epistatic genetic effects and overlapping genetics in autoimmune diseases.
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| 2. |
- Stacey, Simon N, et al.
(författare)
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A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:11, s. 1098-103
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Tidskriftsartikel (refereegranskat)abstract
- To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).
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| 3. |
- Thorleifsdottir, Ragna Hlin, et al.
(författare)
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Patient-reported Outcomes and Clinical Response in Patients with Moderate-to-severe Plaque Psoriasis Treated with Tonsillectomy : A Randomized Controlled Trial
- 2017
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 97:3, s. 340-345
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis is a chronic inflammatory skin disease with profound effects on patients' health-related quality of life (HRQoL). Twenty-nine patients with plaque psoriasis and a history of streptococcal-associated psoriasis exacerbations were randomly assigned to tonsillectomy (n = 15) or control (n = 14) groups and followed for 24 months. Patients were evaluated with the Psoriasis Disability Index, Psoriasis Life Stress Inventory and Psoriasis Area and Severity Index. HRQoL and psoriasis-related stress improved significantly in the tonsillectomy group compared with the control group (p = 0.037 and p = 0.002, respectively), with a mean 50% improvement in HRQoL and a mean 59% improvement in psoriasis-induced stress. Clinical improvement correlated significantly with improved HRQoL (r = 0.297, p = 0.008) and psoriasis-related stress (r = 0.310, p = 0.005). Of the tonsillectomized patients, 87% concluded that the procedure was worthwhile. Tonsillectomy may improve quality of life for selected patients with plaque psoriasis.
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| 4. |
- Thorleifsdottir, Ragna H., et al.
(författare)
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Throat Infections are Associated with Exacerbation in a Substantial Proportion of Patients with Chronic Plaque Psoriasis
- 2016
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 96:6, s. 788-791
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcal throat infections are known to trigger or exacerbate psoriasis, and several studies support the benefit of tonsillectomy. To evaluate the potential of tonsillectomy as a treatment, we used a retrospective study-specific questionnaire to assess the proportion of psoriasis patients with sore throat-associated psoriasis exacerbations. Our survey sampled 275 psoriasis patients. Of patients with plaque psoriasis, 42% reported sore throat-associated psoriasis exacerbations, and of patients with confirmed streptococcal infections, 72% reported aggravation. Notably, women and patients with early onset psoriasis were more likely to report psoriasis exacerbation after a sore throat (p< 0.001, p = 0.046, respectively). Other psoriasis aggravation factors were more common in patients with sore throat-associated exacerbations (p < 0.01). Of tonsillectomized patients, 49% reported subsequent improvement and had more frequent sore throat -associated aggravation of psoriasis than patients who did not improve after tonsillectomy (p=0.015). These findings suggest a closer association between sore throats, streptococcal throat infections and plaque psoriasis than reported previously.
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