Background/objectives: Acute pancreatitis (AP) is one of the most common gastrointestinal disorders often requiring hospitalization. Frequent aetiologies are gallstones and alcohol abuse. In contrast to chronic pancreatitis (CP) few robust genetic associations have been described. Here we analysed whether common variants in the CLDN2-MORC4 and the PRSS1-PRSS2 locus that increase recurrent AP and CP risk associate with AP.
Methods: We screened 1462 AP patients and 3999 controls with melting curve analysis for SNPs rs10273639 (PRSS1-PRSS2), rs7057398 (RIPPLY), and rs12688220 (MORC4). Calculations were performed for the overall group, aetiology, and gender sub-groups. To examine genotype-phenotype relationships we performed several meta-analyses.
Results: Meta-analyses of all AP patients depicted significant (p-value < 0.05) associations for rs10273639 (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.81-0.97, p-value 0.01), rs7057398 (OR 1.27, 95% CI 1.07-1.5, p-value 0.005), and rs12688220 (OR 1.32, 95% CI 1.12-1.56, p-value 0.001). For the different aetiology groups a significant association was shown for rs10273639 (OR 0.76, 95% CI 0.63-0.92, p-value 0.005), rs7057398 (OR 1.43, 95% CI 1.07-1.92, p-value 0.02), and rs12688220 (OR 1.44, 95% CI 1.07-1.93, p-value 0.02) in the alcoholic sub-group only.
Conclusions: The association of CP risk variants with different AP aetiologies, which is strongest in the alcoholic AP group, might implicate common pathomechanisms most likely between alcoholic AP and CP.
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http://dx.doi.org/10.1016/j.pan.2018.05.486 | DOI Listing |
JCO Precis Oncol
January 2025
Karmanos Cancer Institute and Department of Oncology, Wayne State University School of Medicine, Detroit, MI.
Purpose: Although lung cancer is one of the most common malignancies, the underlying genetics regarding susceptibility remain poorly understood. We characterized the spectrum of pathogenic/likely pathogenic (P/LP) germline variants within DNA damage response (DDR) genes among lung cancer cases and controls in non-Hispanic Whites (NHWs) and African Americans (AAs).
Materials And Methods: Rare, germline variants in 67 DDR genes with evidence of pathogenicity were identified using the ClinVar database.
Int J Rheum Dis
January 2025
Department of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Hubei, China.
Objective: Osteoarthritis is a common joint disease caused by a variety of risk factors, and it has been found that many biochemical markers are abnormal in peripheral blood and urine of patients with OA. The aim of this study was to elucidate the causal relationship between biomarkers associated with these processes and OA using Mendelian randomization (MR) analysis.
Method: The inverse variance weighted (IVW) approach to MR was primarily used to explore causal associations between exposures and outcomes using publicly available genetic variants from large genome-wide association studies (GWAS).
Mol Genet Genomic Med
January 2025
College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
Background: The use of exome sequencing (ES) has helped in detecting many variants and genes that cause primary adrenal insufficiency (PAI). The diagnosis of PAI is difficult and can be life-threatening if not treated urgently. Consanguinity can impact the detection of recessively inherited genes.
View Article and Find Full Text PDFAnn Neurol
January 2025
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
Unlabelled: Congenital titinopathy has recently emerged as one of the most common congenital muscle disorders.
Objective: To better understand the presentation and clinical needs of the under-characterized extreme end of the congenital titinopathy severity spectrum.
Methods: We comprehensively analyzed the clinical, imaging, pathology, autopsy, and genetic findings in 15 severely affected individuals from 11 families.
J Pathol
January 2025
SIREDO Oncology Center (Care, Innovation and Research for Children and AYA with Cancer), Institut Curie, Université Paris Cité, Paris, France.
Rhabdoid tumours (RT) are an aggressive malignancy affecting <2-year-old infants, characterised by biallelic loss-of-function alterations in SWI/SNF-related BAF chromatin remodelling complex subunit B1 (SMARCB1) in nearly all cases. Germline SMARCB1 alterations are found in ~30% of patients and define the RT Predisposition Syndrome type 1 (RTPS1). Uveal melanoma (UVM), the most common primary intraocular cancer in adults, does not harbour SMARCB1 alterations.
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