Whole Exome Sequencing Identified Two Single Nucleotide Polymorphisms of Human Leukocyte Antigen-DRB5 in Familial Sarcoidosis in China.
Curr Gene Ther
; 23(3): 215-227, 2023.
Article
in En
| MEDLINE
| ID: mdl-36658707
ABSTRACT
BACKGROUND:
Sarcoidosis is a multisystem granulomatous disorder whose etiology is related to genetic and immunological factors. Familial aggregation and ethnic prevalence suggest a genetic predisposition and inherited susceptibility to sarcoidosis.OBJECTIVE:
This study aimed to identify suspected risk loci for familial sarcoidosis patients.METHODS:
We conducted whole exome sequencing on two sarcoidosis patients and five healthy family members in a Chinese family for a case-control study. The two sarcoidosis patients were siblings who showed chronic disease.RESULTS:
The Gene Ontology results showed single nucleotide polymorphisms in three genes, including human leukocyte antigen (HLA)-DRB1, HLA-DRB5, and KIR2DL4, associated with both 'antigen processing and presentation' and 'regulation of immune response.' Sanger sequencing verified two nonsynonymous mutations in HLA-DRB5 (rs696318 and rs115817940) located on 6p21.3 in the major histocompatibility complex (MHC) class II beta 1 region. The structural model simulated on Prot- Param protein analysis by the Expert Protein Analysis System predicted that the hydropathy index changed at two mutation sites (rs696318 p.F96L, -1.844 to -1.656 and rs115817940 p.T106N, -0.322 to -0.633), which indicated the probability of changes in peptide-binding selectivity.CONCLUSION:
Our results indicated that two nonsynonymous mutations of HLA-DRB5 have been identified in two sarcoidosis siblings, while their healthy family members do not have the mutations. The two HLA-DRB5 alleles may influence genetic susceptibility and chronic disease progression through peptide mutations on the MHC class II molecule among the two affected family members.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sarcoidosis
/
Polymorphism, Single Nucleotide
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Curr Gene Ther
Journal subject:
GENETICA MEDICA
/
TERAPEUTICA
Year:
2023
Document type:
Article