RESUMO
We tested 310,605 SNPs for association in 778 individuals with celiac disease and 1,422 controls. Outside the HLA region, the most significant finding (rs13119723; P = 2.0 x 10(-7)) was in the KIAA1109-TENR-IL2-IL21 linkage disequilibrium block. We independently confirmed association in two further collections (strongest association at rs6822844, 24 kb 5' of IL21; meta-analysis P = 1.3 x 10(-14), odds ratio = 0.63), suggesting that genetic variation in this region predisposes to celiac disease.
Assuntos
Doença Celíaca/genética , Predisposição Genética para Doença , Variação Genética , Genoma Humano , Interleucina-2/genética , Interleucinas/genética , Animais , Cromossomos Humanos Par 4/genética , Humanos , Desequilíbrio de Ligação , Camundongos , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
AIM: To assess the level of undiagnosed coeliac disease (CD) in relatives of patients affected by the condition. METHODS: We collected blood from 914 relatives of probands. We screened these individuals by ELISA for IgA and IgG tTG antibodies, confirming any positive IgA tTG results with an IgA EMA and looked for evidence of IgA deficiency in those who were IgG tTG positive alone, and performed IgG1 EMA in these individuals. We undertook HLA typing where positive screening was found, and this confirmed a strong prevalence of HLA-DQ2 in the coeliac population. Follow-up small intestinal biopsy was undertaken in cases with positive serological screening, wherever possible. RESULTS: Use of this serological screening algorithm revealed a prevalence of undiagnosed CD in 5%-6% of first degree relatives of probands. CONCLUSION: Our data suggests that first degree relatives of individuals with CD should be screened for this condition.
Assuntos
Algoritmos , Doença Celíaca/diagnóstico , Doença Celíaca/genética , Testes Genéticos/métodos , Adulto , Biópsia , Doença Celíaca/sangue , Doença Celíaca/patologia , Feminino , Antígenos HLA-DQ/sangue , Antígenos HLA-DQ/genética , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Intestino Delgado/patologia , Masculino , Pessoa de Meia-Idade , Linhagem , Prevalência , Transglutaminases/genética , Transglutaminases/imunologiaRESUMO
BACKGROUND & AIMS: Ulcerative colitis (UC) is largely a disease of nonsmokers in which transdermal nicotine improves the symptoms but often causes adverse events (AEs). Nicotine enemas cause fewer AEs and were used as supplemental treatment for active UC. METHODS: We treated 104 patients with active UC with either 6-mg nicotine enemas or placebo enemas for 6 weeks in a randomized double-blind study. Patients continued their oral therapy, if any, for UC: 68 patients were taking mesalamine, 15 patients were taking prednisolone, and 12 patients were taking thiopurines during the study. Clinical, sigmoidoscopic, and histologic assessments were made at baseline and at the end of the study and symptoms were recorded daily on a diary card. The primary end point was induction of clinical remission and clinical improvement also was measured by the UC disease activity index. After the study, patients then used nicotine enemas daily for 4 weeks and sigmoidoscopy with a biopsy examination was repeated. AEs and salivary cotinine levels were monitored throughout the study. RESULTS: Clinical remission was achieved in 14 of 52 (27%) patients on active treatment and 14 of 43 (33%) patients on placebo (P = .55). The UC disease activity index improved by 1.45 points in the active group and by 1.65 points for those on placebo (P = .88). Only 1 patient discontinued treatment because of an AE (abdominal pain). In the 47 patients taking mesalamine only, active treatment conferred benefit that was not statistically significant; disease remission occurred in 9 of 25 patients on active therapy and 4 of 21 patients on placebo (P = .20). CONCLUSIONS: Six-milligram nicotine enemas were well tolerated but were not found to be efficacious for active UC.