16 research outputs found
Genetic Variants of Wnt Transcription Factor TCF-4 (TCF7L2) Putative Promoter Region Are Associated with Small Intestinal Crohn's Disease
Reduced expression of Paneth cell antimicrobial α-defensins, human defensin (HD)-5 and -6, characterizes Crohn's disease (CD) of the ileum. TCF-4 (also named TCF7L2), a Wnt signalling pathway transcription factor, orchestrates Paneth cell differentiation, directly regulates the expression of HD-5 and -6, and was previously associated with the decrease of these antimicrobial peptides in a subset of ileal CD. To investigate a potential genetic association of TCF-4 with ileal CD, we sequenced 2.1 kb of the 5′ flanking region of TCF-4 in a small group of ileal CD patients and controls (n = 10 each). We identified eight single nucleotide polymorphisms (SNPs), of which three (rs3814570, rs10885394, rs10885395) were in linkage disequilibrium and found more frequently in patients; one (rs3814570) was thereby located in a predicted regulatory region. We carried out high-throughput analysis of this SNP in three cohorts of inflammatory bowel disease (IBD) patients and controls. Overall 1399 healthy individuals, 785 ulcerative colitis (UC) patients, 225 CD patients with colonic disease only and 784 CD patients with ileal involvement were used to determine frequency distributions. We found an association of rs3814570 with ileal CD but neither with colonic CD or UC, in a combined analysis (allele positivity: OR 1.27, 95% CI 1.07 to 1.52, p = 0.00737), which was the strongest in ileal CD patients with stricturing behaviour (allele frequency: OR 1.32, 95% CI 1.08 to1.62, p = 0.00686) or an additional involvement of the upper GIT (allele frequency: OR 1.38, 95% CI 1.03 to1.84, p = 0.02882). The newly identified genetic association of TCF-4 with ileal CD provides evidence that the decrease in Paneth cell α-defensins is a primary factor in disease pathogenesis
Retinal Vascular Occlusion after COVID-19 Vaccination : More Coincidence than Causal Relationship? Data from a Retrospective Multicentre Study
Background: To investigate whether vaccination against SARS-CoV-2 is associated with
the onset of retinal vascular occlusive disease (RVOD). Methods: In this multicentre study, data
from patients with central and branch retinal vein occlusion (CRVO and BRVO), central and branch
retinal artery occlusion (CRAO and BRAO), and anterior ischaemic optic neuropathy (AION) were
retrospectively collected during a 2-month index period (1 June–31 July 2021) according to a defined
protocol. The relation to any previous vaccination was documented for the consecutive case series.
Numbers of RVOD and COVID-19 vaccination were investigated in a case-by-case analysis. A case–
control study using age- and sex-matched controls from the general population (study participants
from the Gutenberg Health Study) and an adjusted conditional logistic regression analysis was
conducted. Results: Four hundred and twenty-one subjects presenting during the index period
(61 days) were enrolled: one hundred and twenty-one patients with CRVO, seventy-five with BRVO,
fifty-six with CRAO, sixty-five with BRAO, and one hundred and four with AION. Three hundred
and thirty-two (78.9%) patients had been vaccinated before the onset of RVOD. The vaccines given
were BNT162b2/BioNTech/Pfizer (n = 221), followed by ChadOx1/AstraZeneca (n = 57), mRNA1273/Moderna (n = 21), and Ad26.COV2.S/Johnson & Johnson (n = 11; unknown n = 22). Our
case–control analysis integrating population-based data from the GHS yielded no evidence of an
increased risk after COVID-19 vaccination (OR = 0.93; 95% CI: 0.60–1.45, p = 0.75) in connection with
a vaccination within a 4-week window. Conclusions: To date, there has been no evidence of any
association between SARS-CoV-2 vaccination and a higher RVOD risk