Electrostatic Modifications of HLA-DR Peptide-Binding Pocket and PSC Susceptibility
Author Information
Author(s): Hov Johannes R, Kosmoliaptsis Vasilis, Traherne James A, Olsson Marita, Boberg Kirsten M, Bergquist Annika, Schrumpf Erik, Bradley J Andrew, Taylor Craig J, Lie Benedicte A, Trowsdale John, Karlsen Tom H
Primary Institution: Norwegian PSC Research Center, Clinic for Specialized Medicine and Surgery, Oslo University Hospital Rikshospitalet
Hypothesis
How do variations in the HLA-DRB1 gene influence susceptibility to primary sclerosing cholangitis (PSC)?
Conclusion
Residues 37 and 86 of the HLA-DRβ chain significantly influence the electrostatic properties of pocket P9, affecting the range of peptides presented and susceptibility to PSC.
Supporting Evidence
- Residue 37 was identified as a major determinant of the electrostatic properties of pocket P9.
- Carriers of asparagine at residue 37 had a significantly higher risk of PSC.
- Residue 86 also influenced the electrostatic properties of pocket P9.
Takeaway
This study found that certain parts of a protein related to the immune system can change how the body reacts to diseases like PSC, making some people more likely to get sick.
Methodology
Four-digit HLA-DRB1 genotyping was performed in 356 PSC patients and 366 healthy controls, followed by logistic regression analyses.
Limitations
The study may not account for all genetic factors influencing PSC due to strong linkage disequilibrium in the HLA region.
Participant Demographics
356 PSC patients (71% male, median age 36) and 366 healthy controls (70% male).
Statistical Information
P-Value
1.2 × 10−32
Confidence Interval
95% CI 4.0-8.0 for Asn37
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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