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Angiogenesis-related gene expression analysis in celiac disease
Ainara Castellanos-Rubio1, Sergio Caja, Iñaki Irastorza
1Immunogenetics Research Laboratory, Endocrinology, Diabetes and Nutrition Research Group, Hospital de Cruces, Barakaldo, Basque Country.
Autoimmunity
|December 6, 2011
Summary
Genetic variants and gene expression changes in celiac disease (CD) reveal complex angiogenesis disturbances. Transglutaminase autoantibodies (TGA) influence gene expression, highlighting TGM2 and PML as antiangiogenic factors in CD pathogenesis.
Area of Science:
- Immunology
- Genetics
- Gastroenterology
Background:
- Celiac disease (CD) is linked to small-bowel vascular network disturbances.
- Transglutaminase autoantibodies (TGA) are implicated in angiogenesis dysregulation.
- Genetic variants in angiogenesis-related genes may influence CD pathogenesis.
Purpose of the Study:
- Investigate genetic and functional roles of angiogenesis-related genes in celiac disease.
- Analyze gene expression changes in intestinal biopsies and cell models.
- Determine the impact of TGA on angiogenesis-related gene expression.
Main Methods:
- Genotyping of single nucleotide polymorphisms (SNPs) in 555 CD patients and 541 controls.
- Quantification of gene expression in intestinal biopsies (CD vs. gluten-free diet) and cell cultures (HUVEC, T84).
- Incubation of cell cultures with TGA-positive and negative serum.
Main Results:
- A TNFSF13 SNP (rs11552708) associated with CD (p=0.01, OR=0.7).
- TGM2 and PML identified as upregulated antiangiogenic genes; GNA13, TGFA, ERBB2, SCG2 as downregulated proangiogenic factors in CD biopsies.
- TGA enhanced TGM2 expression in both cell models; differential effects on PML, GNA13, and ERBB2 expression observed.
Conclusions:
- Genetic and expression data reveal complex angiogenesis alterations in celiac disease.
- TGA significantly influence angiogenesis-related gene expression.
- Cell culture models aid in dissecting complex gene interactions in CD pathogenesis.
