Background: Graves' disease (GD) is a complex disease in which genetic predisposition is modified by environmental factors. Each gene exerts limited effects on the development of autoimmune disease (OR = 1.2-1.5). An epidemiological study revealed that nearly 70% of the risk of developing inherited autoimmunological thyroid diseases (AITD) is the result of gene interactions. In the present study, we analyzed the effects of the interactions of multiple loci on the genetic predisposition to GD. The aim of our analyses was to identify pairs of genes that exhibit a multiplicative interaction effect.
Material And Methods: A total of 709 patients with GD were included in the study. The patients were stratified into more homogeneous groups depending on the age at time of GD onset: younger patients less than 30 years of age and older patients greater than 30 years of age. Association analyses were performed for genes that influence the development of GD: HLADRB1, PTPN22, CTLA4 and TSHR. The interactions among polymorphisms were analyzed using the multiple logistic regression and multifactor dimensionality reduction (MDR) methods.
Results: GD patients stratified by the age of onset differed in the allele frequencies of the HLADRB1*03 and 1858T polymorphisms of the PTPN22 gene (OR = 1.7, p = 0.003; OR = 1.49, p = 0.01, respectively). We evaluated the genetic interactions of four SNPs in a pairwise fashion with regard to disease risk. The coexistence of HLADRB1 with CTLA4 or HLADRB1 with PTPN22 exhibited interactions on more than additive levels (OR = 3.64, p = 0.002; OR = 4.20, p < 0.001, respectively). These results suggest that interactions between these pairs of genes contribute to the development of GD. MDR analysis confirmed these interactions.
Conclusion: In contrast to a single gene effect, we observed that interactions between the HLADRB1/PTPN22 and HLADRB1/CTLA4 genes more closely predicted the risk of GD onset in young patients.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4778933 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0150307 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
Machine Learning-Based Real-Time Survival Prediction for Gastric Neuroendocrine Carcinoma.
Ann Surg Oncol
January 2025
Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Background: This study aimed to develop a dynamic survival prediction model utilizing conditional survival (CS) analysis and machine learning techniques for gastric neuroendocrine carcinomas (GNECs).
Patients And Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015) were analyzed and split into training and validation groups (7:3 ratio). CS profiles for patients with GNEC were examined in the full cohort.
Hematopoietic stem cell transplantation and immunosuppressive therapy: implications of clonal haematopoiesis.
Ann Hematol
January 2025
Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China.
Aplastic anemia (AA) is a life-threatening bone marrow failure syndrome. The advent of next-generation sequencing (NGS) has shed light on the link between somatic mutations (SM) and the efficacy of immunosuppressive therapy (IST) in AA patients. However, the relationship between SM and hematopoietic stem cell transplantation (HSCT) has not been extensively explored.
View Article and Find Full Text PDFPelvic ring fracture and erectile dysfunction (PERFECD) - 3 year follow-up cross sectional study.
Eur J Trauma Emerg Surg
January 2025
Faculty of Medicine, University of Zurich, Raemistrasse 71, 8006, Zurich, Switzerland.
Introduction: Pelvic ring fractures are known to be associated with complications associated with adjacent organ injuries, such as the urogenital tract (e.g. erectile dysfunction (ED), which are sometimes diagnosed in a delayed fashion.
View Article and Find Full Text PDFCancer risk in carriers of TP53 germline variants grouped into different functional categories.
JNCI Cancer Spectr
January 2025
Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Li-Fraumeni syndrome is a cancer predisposition syndrome caused by pathogenic TP53 germline variants and associated with a high lifelong cancer risk. We analysed the German LFS registry that contains data on 304 individuals. Cancer phenotypes were correlated with variants grouped according to their ability to transactivate target genes in a yeast assay using a traditional (non-functional, partially-functional) and a novel (clusters A, B, C) classification of variants into different groups.
View Article and Find Full Text PDFTo determine whether tailored interventions based on patients' psychological profiles enhanced the outcomes of interventions in people with nonspecific low back pain, compared to usual care. Intervention systematic review with meta-analysis. Embase, Cochrane, Medline, Web of Science, CINAHL, and PsycINFO were searched from their inception until November 2, 2023.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!