| 11. |
- 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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| 12. |
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| 13. |
- Meraviglia, Viviana, et al.
(författare)
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Higher cardiogenic potential of iPSCs derived from cardiac versus skin stromal cells
- 2016
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Ingår i: Frontiers in Bioscience. - 1093-9946 .- 1093-4715. ; 21, s. 719-43
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Tidskriftsartikel (refereegranskat)abstract
- Prior studies have demonstrated that founder cell type could influence induced pluripotent stem cells (iPSCs) molecular and developmental properties at early passages after establishing their pluripotent state. Herein, we evaluated the persistence of a functional memory related to the tissue of origin in iPSCs from syngeneic cardiac (CStC) vs skin stromal cells (SStCs). We found that, at passages greater than 15, iPSCs from cardiac stromal cells (C-iPSCs) produced a higher number of beating embryoid bodies than iPSCs from skin stromal cells (S-iPSCs). Flow cytometry analysis revealed that dissected beating areas from C-iPSCs exhibited more Troponin-T positive cells compared to S-iPSCs. Beating areas derived from C-iPSCs displayed higher expression of cardiac markers, more hyperpolarized diastolic potentials, larger action potential amplitude and higher contractility than beaters from skin. Also, different microRNA subsets were differentially modulated in CStCs vs SStCs during the reprogramming process, potentially accounting for the higher cardiogenic potentials of C-iPSCs vs S-iPSCs. Therefore, the present work supports the existence of a founder organ memory in iPSCs obtained from the stromal component of the origin tissue.
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| 14. |
- Motta, Benedetta M., et al.
(författare)
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Microbiota, type 2 diabetes and non-alcoholic fatty liver disease : protocol of an observational study
- 2019
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Ingår i: Journal of Translational Medicine. - : BMC. - 1479-5876 .- 1479-5876. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by triglyceride accumulation in the hepatocytes in the absence of alcohol overconsumption, commonly associated with insulin resistance and obesity. Both NAFLD and type 2 diabetes (T2D) are characterized by an altered microbiota composition, however the role of the microbiota in NAFLD and T2D is not well understood. To assess the relationship between alteration in the microbiota and NAFLD while dissecting the role of T2D, we established a nested study on T2D and non-T2D individuals within the Cooperative Health Research In South Tyrol (CHRIS) study, called the CHRIS-NAFLD study. Here, we present the study protocol along with baseline and follow-up characteristics of study participants. Methods: Among the first 4979 CHRIS study participants, 227 individuals with T2D were identified and recalled, along with 227 age- and sex-matched non-T2D individuals. Participants underwent ultrasound and transient elastography examination to evaluate the presence of hepatic steatosis and liver stiffness. Additionally, sampling of saliva and faeces, biochemical measurements and clinical interviews were carried out. Results: We recruited 173 T2D and 183 non-T2D participants (78% overall response rate). Hepatic steatosis was more common in T2D (63.7%) than non-T2D (36.3%) participants. T2D participants also had higher levels of liver stiffness (median 4.8 kPa, interquartile range (IQR) 3.7, 5.9) than non-T2D participants (median 3.9 kPa, IQR 3.3, 5.1). The non-invasive scoring systems like the NAFLD fibrosis score (NFS) suggests an increased liver fibrosis in T2D (mean - 0.55, standard deviation, SD, 1.30) than non-T2D participants (mean - 1.30, SD, 1.17). Discussion: Given the comprehensive biochemical and clinical characterization of study participants, once the bio-informatics classification of the microbiota will be completed, the CHRIS-NAFLD study will become a useful resource to further our understanding of the relationship between microbiota, T2D and NAFLD.
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| 15. |
- Pattaro, Cristian, et al.
(författare)
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The Cooperative Health Research in South Tyrol (CHRIS) study : rationale, objectives, and preliminary results
- 2015
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Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876 .- 1479-5876. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The Cooperative Health Research In South Tyrol (CHRIS) study is a population-based study with a longitudinal lookout to investigate the genetic and molecular basis of age-related common chronic conditions and their interaction with life style and environment in the general population. All adults of the middle and upper Vinschgau/Val Venosta are invited, while 10,000 participants are anticipated by mid-2017. Family participation is encouraged for complete pedigree reconstruction and disease inheritance mapping. After a pilot study on the compliance with a paperless assessment mode, computer-assisted interviews have been implemented to screen for conditions of the cardiovascular, endocrine, metabolic, genitourinary, nervous, behavioral, and cognitive system. Fat intake, cardiac health, and tremor are assessed instrumentally. Nutrient intake, physical activity, and life-course smoking are measured semi-quantitatively. Participants are phenotyped for 73 blood and urine parameters and 60 aliquots per participant are biobanked (cryo-preserved urine, DNA, and whole and fractionated blood). Through liquid-chromatography mass-spectrometry analysis, metabolite profiling of the mitochondrial function is assessed. Samples are genotyped on 1 million variants with the Illumina HumanOmniExpressExome array and the first data release including 4570 fully phenotyped and genotyped samples is now available for analysis. Participants' follow-up is foreseen 6 years after the first visit. The target population is characterized by long-term social stability and homogeneous environment which should both favor the identification of enriched genetic variants. The CHRIS cohort is a valuable resource to assess the contribution of genomics, metabolomics, and environmental factors to human health and disease. It is awaited that this will result in the identification of novel molecular targets for disease prevention and treatment.
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| 16. |
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