| 1. |
- Huffman, Jennifer E., et al.
(författare)
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Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, P-inter= 2.6 x 10(-8)). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDAR-ADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10(-8)), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10(-8)), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10(-4)). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.
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| 2. |
- Kadam, Esha, et al.
(författare)
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Collating the voice of people with autoimmune diseases : Methodology for the Third Phase of the COVAD Studies
- 2024
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Ingår i: Rheumatology International. - : Springer. - 0172-8172 .- 1437-160X.
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The growing recognition of holistic patient care highlights the various factors shaping the quality of life of individuals with autoimmune and rheumatic diseases (AIRDs). Beyond the traditional disease measures, there is an emerging acknowledgment of the less-explored aspects, including subjective well-being, social determinants of health, comorbidities, mental health, and medication adherence. Moreover, digital health services have empowered patients to engage actively in decision-making alongside clinicians. To explore these domains within the context of AIRDs, the "Collating the Voice of People with Autoimmune Diseases" COVAD survey was conceived, a successor of the previous two COVAD surveys. In this document, we present the study protocol in comprehensive detail.METHODS: The COVAD-3 survey is a cross-sectional patient self-reported e-survey incorporating multiple widely accepted scales/scores to assess various aspects of patients' lifestyles objectively. To ensure the survey's accuracy and usability across diverse regions, it will be translated into multiple languages and subjected to rigorous vetting and pilot testing. It will be distributed by collaborators via online platforms and data will be collected from patients with AIRDs, and healthy individuals over eight months. Data analysis will focus on outcome measures related to various social, demographic, economic, and psychological factors.CONCLUSION: With the increasing awareness to adopt a holistic treatment approach encompassing all avenues of life, the COVAD-3 survey aims to gain valuable insights into the impact of social, demographic, economic, and psychological determinants of health on the subjective well-being in patients with AIRDs, which will contribute to a better understanding of their overall health and well-being.
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| 3. |
- Kapetanovic, Meliha C., et al.
(författare)
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The risk of clinically diagnosed gout by serum urate levels : Results from 30 years follow-up of the Malmö preventive project cohort in southern Sweden
- 2018
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hyperuricemia (HU) is in the causal pathway for developing clinical gout. There are few population-based assessments of the absolute and relative risk of clinically diagnosed incident gout in subjects with HU. We aimed to explore the long-term risk of developing incident gout among asymptomatic adults with different levels of serum urate (SU). Methods: Malmö Preventive Project was a population-based screening program for cardiovascular risk factors, alcohol abuse, and breast cancer in Malmö, Sweden. The study population was screened between 1974 and 1992. At baseline, subjects were assessed with a questionnaire, physical examination, and laboratory tests. Follow-up ended at first gout diagnosis, death, moving from area, or December 31, 2014. Incident gout (using ICD10 codes) was diagnosed based on national registers for specialized inpatient and outpatient care, and from 1998 onward in the Skåne Healthcare Register including primary healthcare. Incidence rates, absolute risk, hazard ratios (HRs) and potentially associated factors were analyzed by baseline SU levels, i.e. normal levels (≤ 360 μmol/L); 361-405 (levels below tissue solubility of SU), and > 405 (HU), overall, and by sex. Results: Overall, 1275 individuals [3.8%; 1014 men (4.5%) and 261 women (2.4%)] of the 33,346 study participants (mean age: 45.7 (SD: 7.4), 67% men), developed incident gout during follow-up (mean 28.2 years). Of those with HU, 14.7% of men and 19.5% of women developed gout. Compared to subjects in the lowest SU category, the age-adjusted HR in men increased from 2.7 to 6.4, and in women from 4.4 to 13.1 with increasing baseline SU category, and with a statistically significant interaction of sex (p < 0.001). Body mass index, estimated glomerular filtration rate (negative), triglycerides, alcohol risk behavior (only in men), and comorbidities such as hypertension, cardiovascular disease, and diabetes were strongly associated with SU at baseline in both sexes. Conclusions: The absolute risk for developing clinically diagnosed gout over 30 years in middle-aged subjects was 3.8%, and increased progressively in both men and women in relation to baseline SU. This risk increase was significantly higher in women than in men, whereas the associations between baseline risk markers and SU levels were similar in both sexes.
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