scholarly journals The Impact of PPARγGenetic Variants on IBD Susceptibility and IBD Disease Course

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Jessica Mwinyi ◽  
Christa Grete-Wenger ◽  
Jyrki J. Eloranta ◽  
Gerd A. Kullak-Ublick

PPARγ is a nuclear receptor that regulates numerous pathways including cytokine expression and immune responses and plays an important role in controlling colon inflammation. We aimed at determining the occurringPPARγ SNPs, at predicting the haplotypes, and at determining the frequency outcome in inflammatory bowel disease (IBD) patients in comparison with healthy controls. We determined genetic variants in the coding exons and flanking intronic sequences of theNR1C3gene in 284 IBD patients and 194 controls and predictedNR1C3haplotypes via bioinformatic analysis. We investigated whether certainNR1C3variants are associated with susceptibility to IBD or its disease course. None of the detected 22NR1C3variants were associated with IBD. Two variants with allelic frequencies over 1% were included in haplotype/diplotype analyses. None of theNR3C1haplotypes showed association with IBD development or disease course. We conclude thatNR1C3haplotypes are not related to IBD susceptibility or IBD disease activity.

2019 ◽  
Vol 26 (5) ◽  
pp. 746-755
Author(s):  
Joana Roseira ◽  
Fernando Magro ◽  
Samuel Fernandes ◽  
Carolina Simões ◽  
Francisco Portela ◽  
...  

Abstract Background The impact of inflammatory bowel disease (IBD) on sexual health is a leading concern among patients. Most studies focus on sexual dysfunction rather than patient-perceived sexual quality of life (SQoL). We aimed to assess SQoL in IBD patients compared with healthy controls. Methods This is a multicenter, cross-sectional study of IBD patients (n = 575 with Crohn’s disease and n = 294 with ulcerative colitis), compared with healthy controls (n = 398), that used an anonymous self-administered questionnaire. This multimodal questionnaire included sociodemographic data and 4 validated instruments: Short IBD Questionnaire, Social Desirability Scale, Sexual QoL Questionnaire–Male/Female, Nine-item Patient Health Questionnaire. Results Inflammatory bowel disease patients reported lower SQoL (men: 77.29 vs 83.83; P < 0.001; women: 70.40 vs 81.63; P < 0.001) compared with controls. Among IBD patients, SQoL was positively correlated with health-related quality of life (HRQoL) and negatively correlated with depression symptoms. Perianal disease was associated with lower HRQoL and higher incidence of depression, but only impacted SQoL in men. In linear regression analysis for men, SQoL was associated with age, marital status, and depression (β, –2.101; 95% confidence interval [CI], –2.505 to –1.696; P < 0.001). In women, SQoL was associated with depression (β, –1.973; 95% CI, –2.313 to –1.632; P < 0.001) only. Conclusions Patients with IBD had impaired SQoL compared with healthy controls. Age, widow status, and depression were independent predictors of SQoL in men with IBD, whereas in women depression was the only independent predictor. Emotional and self-esteem issues were the main concerns reported by IBD patients regarding sexual health.


Author(s):  
Kimberly N Weaver ◽  
Xian Zhang ◽  
Xiangfeng Dai ◽  
Runa Watkins ◽  
Jeremy Adler ◽  
...  

Abstract Background Severe acute respiratory syndrome coronavirus 2 vaccination is recommended for all individuals with inflammatory bowel disease (IBD), including those on immunosuppressive therapies; however, little is known about vaccine safety and efficacy in these patients or the impact of vaccination on IBD disease course. Methods We evaluated coronavirus disease 2019 (COVID-19) vaccine–related adverse events (AEs) and the effect of vaccination on IBD disease course among participants in the PREVENT-COVID (Partnership to Report Effectiveness of Vaccination in populations Excluded from iNitial Trials of COVID) study, a prospective, observational cohort study. Localized and systemic reactions were assessed via questionnaire. Disease flare was defined by worsening IBD symptoms and change in IBD medications. Outcomes were stratified by vaccine type and IBD medication classes. Results A total of 3316 individuals with IBD received at least 1 COVID-19 vaccine. Injection site tenderness (68%) and fatigue (46% dose 1, 68% dose 2) were the most commonly reported localized and systemic AEs after vaccination. Severe localized and systemic vaccine-related AEs were rare. The mRNA-1273 vaccine was associated with significantly greater severe AEs at dose 2 (localized 4% vs 2%, systemic 15% vs 10%; P < .001 for both). Prior COVID-19 infection, female sex, and vaccine type were associated with severe systemic reactions to dose 1, while age <50 years, female sex, vaccine type, and antitumor necrosis factor and vedolizumab use were associated with severe systemic reactions to dose 2. Overall rates (2%) of IBD flare were low following vaccination. Conclusions Our findings provide reassurance that the severe acute respiratory syndrome coronavirus 2 vaccine is safe and well tolerated among individuals with IBD, which may help to combat vaccine hesitancy and increase vaccine confidence.


2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S156-S158
Author(s):  
M Agrawal ◽  
L Tarassishin ◽  
A Rendon ◽  
C Hillenbrand ◽  
A Debebe ◽  
...  

Abstract Background There are increasing data on changes in intestinal inflammation and microbiome diversity during pregnancy in women with inflammatory bowel disease (IBD) with implications towards individual and offspring immune function. However, differences in intestinal inflammation, as measured by fecal calprotectin (FC) and microbial a-diversity, in consecutive pregnancies are not known. Methods We prospectively enrolled a cohort of women, 37 with IBD and 39 without IBD, during two consecutive pregnancies, and their offspring. We collected serial stool samples and clinical data, and measured FC and bacterial abundance during each trimester of each pregnancy. We further performed correlation analysis between FC in consecutive pregnancies and between microbial a-diversity in consecutive pregnancies among women with and without IBD. Results Compared to healthy controls, IBD pregnancies had significantly lower gestational age at birth and higher frequency of Cesarean section. Mode of delivery, the status of Group B Streptococcus (GBS) infection and GBS infection prophylaxis were significantly associated with the pregnancy order in both IBD and controls (Table). Furthermore, we observed strong correlations of FC (r=0.56, p-value=0.093) and microbial alpha-diversity assessed as operational taxonomic unit (OTU) richness (r=0.88, p=0.0087) between paired consecutive pregnancies in women with IBD, but not in those without IBD (Figure). There were no differences in microbial alpha-diversity using the Shannon and Simpson indices when comparing consecutive pregnancies of women with and without IBD. Conclusion In this study, we demonstrate that intestinal inflammation and microbiome diversity are more conserved in consecutive pregnancies of women with IBD compared to healthy controls. These findings may have implications towards understanding the impact of pregnancy on host-microbiome interactions in IBD as well as the potential impact on offspring health.


Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3589
Author(s):  
Yasser Morsy ◽  
Nathalie Brillant ◽  
Yannick Franc ◽  
Michael Scharl ◽  
Marcin Wawrzyniak ◽  
...  

Background: The single nucleotide polymorphism (SNP) rs1042058 within the gene locus encoding tumor progression locus 2 (TPL2) has been recently identified as a risk gene for inflammatory bowel disease (IBD). TPL2 has been shown to regulate pro-inflammatory signaling and cytokine secretion, while inhibition of TPL2 decreases intestinal inflammation in vivo. However, the clinical and molecular implications of this disease-associated TPL2 variation in IBD patients have not yet been studied. Methods: We analyzed the impact of the IBD-associated TPL2 variation using clinical data of 2145 genotyped patients from the Swiss IBD Cohort Study (SIBDCS). Furthermore, we assessed the molecular consequences of the TPL2 variation in ulcerative colitis (UC) and Crohn’s disease (CD) patients by real-time PCR and multiplex ELISA of colon biopsies or serum, respectively. Results: We found that presence of the SNP rs1042058 within the TPL2 gene locus results in significantly higher numbers of CD patients suffering from peripheral arthritis. In contrast, UC patients carrying this variant feature a lower risk for intestinal surgery. On a molecular level, the presence of the rs1042058 (GG) IBD-risk polymorphism in TPL2 was associated with decreased mRNA levels of IL-10 in CD patients and decreased levels of IL-18 in the intestine of UC patients. Conclusions: Our data suggest that the presence of the IBD-associated TPL2 variation might indicate a more severe disease course in CD patients. These results reveal a potential therapeutic target and demonstrate the relevance of the IBD-associated TPL2 SNP as a predictive biomarker in IBD.


Marine Drugs ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 196
Author(s):  
Muhammad Bilal ◽  
Leonardo Vieira Nunes ◽  
Marco Thúlio Saviatto Duarte ◽  
Luiz Fernando Romanholo Ferreira ◽  
Renato Nery Soriano ◽  
...  

Naturally occurring biological entities with extractable and tunable structural and functional characteristics, along with therapeutic attributes, are of supreme interest for strengthening the twenty-first-century biomedical settings. Irrespective of ongoing technological and clinical advancement, traditional medicinal practices to address and manage inflammatory bowel disease (IBD) are inefficient and the effect of the administered therapeutic cues is limited. The reasonable immune response or invasion should also be circumvented for successful clinical translation of engineered cues as highly efficient and robust bioactive entities. In this context, research is underway worldwide, and researchers have redirected or regained their interests in valorizing the naturally occurring biological entities/resources, for example, algal biome so-called “treasure of untouched or underexploited sources”. Algal biome from the marine environment is an immense source of excellence that has also been demonstrated as a source of bioactive compounds with unique chemical, structural, and functional features. Moreover, the molecular modeling and synthesis of new drugs based on marine-derived therapeutic and biological cues can show greater efficacy and specificity for the therapeutics. Herein, an effort has been made to cover the existing literature gap on the exploitation of naturally occurring biological entities/resources to address and efficiently manage IBD. Following a brief background study, a focus was given to design characteristics, performance evaluation of engineered cues, and point-of-care IBD therapeutics of diverse bioactive compounds from the algal biome. Noteworthy potentialities of marine-derived biologically active compounds have also been spotlighted to underlying the impact role of bio-active elements with the related pathways. The current review is also focused on the applied standpoint and clinical translation of marine-derived bioactive compounds. Furthermore, a detailed overview of clinical applications and future perspectives are also given in this review.


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