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Genetic background of anticyclic citrullinated peptide autoantibody production in Hungarian patients with rheumatoid arthritis.
- Source :
-
Annals of the New York Academy of Sciences [Ann N Y Acad Sci] 2007 Sep; Vol. 1110, pp. 23-32. - Publication Year :
- 2007
-
Abstract
- Polymorphisms of the peptidylarginine deiminase 4 (PADI4) gene encoding for the isoenzyme that converts arginyl into citrullyl residues have been shown to contribute to susceptibility to rheumatoid arthritis (RA), depending on the population studied. We aimed at determining whether PADI4 single nucleotide polymorphisms (SNPs) are associated with RA in a Hungarian population. The relationship between anticyclic citrullinated peptide (anti-CCP) production and HLA-DRB1 alleles encoding the shared epitope (SE) was also investigated. DNA samples were obtained from RA (n = 261) patients and from control donors (n = 120). HLA-DRB1 genotyping was carried out by polymerase chain reaction (PCR) with sequence-specific priming. PAD4_92 G/C and PAD4_104 T/C SNPs were genotyped using real-time PCR allele discrimination. Autoantibodies against CCP were detected by ELISA. All healthy controls tested anti-CCP negative, whereas 171 (66%) RA patients were anti-CCP positive. No significant difference in allele or genotype frequencies were found between RA patients and controls for any of the PADI4 SNPs. Anti-CCP seropositivity was unrelated to these two SNPs. No association was found between any of the PADI4 SNPs and HLA-DRB1 subtypes. Presence of the HLA-RB1 SE alleles was significantly associated with anti-CCP seropositivity; HLA-DRB1*0401 and HLA-DRB1*1001 carriers showed the strongest association. In conclusion, our data suggest that polymorphisms of the PADI4 gene are not associated with rheumatoid arthritis and are unlikely to be responsible for the presence of anti-CCP autoantibodies in a white Hungarian population. HLA-DRB1 SE alleles, however, may significantly contribute to the genetic determination of anti-CCP production in Hungarian patients with RA.
- Subjects :
- Adult
Aged
Aged, 80 and over
Alleles
Arthritis, Rheumatoid blood
Arthritis, Rheumatoid epidemiology
Autoantibodies blood
Epitopes immunology
Female
Genotype
HLA-DR Antigens immunology
HLA-DRB1 Chains
Humans
Hungary epidemiology
Hydrolases genetics
Male
Middle Aged
Polymorphism, Single Nucleotide genetics
Protein-Arginine Deiminase Type 4
Protein-Arginine Deiminases
Arthritis, Rheumatoid genetics
Arthritis, Rheumatoid immunology
Autoantibodies biosynthesis
Autoantibodies immunology
Peptides, Cyclic genetics
Peptides, Cyclic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0077-8923
- Volume :
- 1110
- Database :
- MEDLINE
- Journal :
- Annals of the New York Academy of Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 17911417
- Full Text :
- https://doi.org/10.1196/annals.1423.004