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- Rivas, Manuel A., et al.
(författare)
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A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis
- 2016
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Ingår i: Nature Communications. - London, United Kingdom : Nature Publishing Group. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF=up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P=6.89 × 10(-7), odds ratio=0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain.
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- Saavalainen, L, et al.
(författare)
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Mortality of midlife women with surgically verified endometriosis-a cohort study including 2.5 million person-years of observation
- 2019
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Ingår i: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 34:8, s. 1576-1586
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTIONIs all-cause and cause-specific mortality increased among women with surgically verified endometriosis?SUMMARY ANSWERThe all-cause and cause-specific mortality in midlife was lower throughout the follow-up among women with surgically verified endometriosis compared to the reference cohort.WHAT IS KNOWN ALREADYEndometriosis has been associated with an increased risk of comorbidities such as certain cancers and cardiovascular diseases. These diseases are also common causes of death; however, little is known about the mortality of women with endometriosis.STUDY DESIGN, SIZE, DURATIONA nationwide retrospective cohort study of women with surgically verified diagnosis of endometriosis was compared to the reference cohort in Finland (1987–2012). Follow-up ended at death or 31 December 2014. During the median follow-up of 17 years, 2.5 million person-years accumulated.PARTICIPANTS/MATERIALS, SETTING, METHODSForty-nine thousand nine hundred and fifty-six women with at least one record of surgically verified diagnosis of endometriosis in the Finnish Hospital Discharge Register between 1987 and 2012 were compared to a reference cohort of 98 824 age- and municipality-matched women. The age (mean ± standard deviation) of the endometriosis cohort was 36.4 ± 9.0 and 53.6 ± 12.1 years at the beginning and at the end of the follow-up, respectively. By using the Poisson regression models the crude and adjusted all-cause and cause-specific mortality rate ratios (MRR) and 95% confidence intervals (CI) were assessed. Calendar time, age, time since the start of follow-up, educational level, and parity adjusted were considered in the multivariate analyses.MAIN RESULTS AND THE ROLE OF CHANCEA total of 1656 and 4291 deaths occurred in the endometriosis and reference cohorts, respectively. A lower all-cause mortality was observed for the endometriosis cohort (adjusted MRR, 0.73 [95% CI 0.69 to 0.77])—there were four deaths less per 1000 women over 10 years. A lower cause-specific mortality contributed to this: the adjusted MRR was 0.88 (95% CI 0.81 to 0.96) for any cancer and 0.55 (95% CI 0.47 to 0.65) for cardiovascular diseases, including 0.52 (95% CI 0.42 to 0.64) for ischemic heart disease and 0.60 (95% CI 0.47 to 0.76) for cerebrovascular disease. Mortality due to alcohol, accidents and violence, respiratory, and digestive disease-related causes was also decreased.LIMITATIONS, REASONS FOR CAUSATIONThese results are limited to women with endometriosis diagnosed by surgery. In addition, the study does not extend into the oldest age groups. The results might be explained by the characteristics and factors related to women’s lifestyle, and/or increased medical attention and care received, rather than the disease itself.WIDER IMPLICATIONS OF THE FINDINGSThese reassuring data are valuable to women with endometriosis and to their health care providers. Nonetheless, more studies are needed to address the causality.STUDY FUNDING/COMPETING INTERESTThis research was funded by the Hospital District of Helsinki and Uusimaa and The Finnish Medical Foundation. None of the authors report any competing interest in relation to the present work; all the authors have completed the disclosure form.
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