HLA-DRB1 and HLA-DQB1 allele associations in an Albanian patient population with rheumatoid arthritis: correlations with the specific autoantibody markers and inter-population DRB1 allele frequency variability

Abstract

The prevalence of rheumatoid arthritis and its specific autoantibodies varies in different populations. This variability depends on the genetic polymorphism of the immune response genes among which the HLA system plays a major role. In this context, we studied the HLA-DRB1 and HLA-DQB1 first-level allele frequencies in 100 Albanian patients with rheumatoid arthritis (RA), and taking into account their rheumatoid factor (RF) and anticitrullinated peptide antibodies (ACPA) serologic subgroups, we compared them with the respective frequencies in a population of 191 Albanian individuals without known pathology. No differences were found between the controls and the RA patient group as a whole, but three statistically significant differences were found: an increase in DRB1*04 among ACPA+, RF+ and ACPA+/RF+ patients, a significant decrease in DRB1*11 among ACPA+/RF+ and also a decrease in DRB1*13 among RF+ patient subgroups. Comparing allele frequencies of putatively associated RA alleles in different European populations revealed a significant negative correlation between the RA predisposing DRB1*04 and protective DRB1*11 allele frequencies. A statistically significant correlation was also found between RA prevalence rates and DRB1*04 as well as DRB1*11 frequencies. The relatively low frequencies of DRB1*04 and high DRB1*11 in the Albanian population might explain the rather low positivity rate of ACPA and RF antibodies among the Albanian RA patients. These specific association patterns suggest that this first study of RA in an Albanian population should be followed up to include second level or higher definition of HLA alleles and to compare RA patterns among European populations.

Association of HLA class II alleles/haplotypes and amino acid variations in the peptide binding pockets with rheumatoid arthritis

“…The increased frequencies of allele DQB1*03:01 (OR = 3.09) and DQB1*06:01 (OR = 2.54) revealed susceptible associations in RA. Our data are in concordance with the previous report that documented an increased susceptible association of alleles DQB1*03 and DQB1*05, while DQB1*06 with a protective association in Moroccan, Han, Albanian populations . The alleles DQB1*05:01 and *05:02 showed a protective association in the present study.…”

Association of Human Leukocyte Antigen (HLA) class II (DRB1 and DQB1) alleles and haplotypes with Rheumatoid Arthritis in Sudanese patients

“…We also found that both alleles were statistically associated with ACPA seropositivity, which is consistent with studies in populations with different ethnicity ( 7 , 25 – 28 ). Furthermore, strong evidence suggests that some HLA-DRB1 alleles, including HLA-DRB1*01 , *04 , and *10 , were associated with the structural severity of RA, and were likely related to the production of ACPA by influencing the antigen presentation ( 29 , 30 ).…”

“…HLA-DRQ1*02 and *06 were found protective against RA in the Albanian population ( 28 ), while in the Kurdi population, these alleles showed a susceptible effect to RA ( 37 ). Other studies in the Turkish population failed to prove any association ( 33 ).…”

Epidemiology of Rheumatoid Arthritis in Southern Albania

“…A recent genetic study investigated the HLA-DRB1 and HLA-DQB1 first-level allele frequencies in Albanian patients with RA, taking into account their rheumatoid factor (RF) and anticitrullinated peptide antibodies (ACPA) serologic subgroups. The study found relatively low frequencies of DRB1*04 and high DRB1*11 in the Albanian population that may explain the rather low positivity rate of ACPA and RF antibodies among Albanian patients with RA ( 20 ). Since both ACPA and RF antibodies are frequently associated with RA and causally involved in the genesis of the disease ( 21 ), the frequency of these alleles may explain the low occurrence of RA in our patients.…”