Epidemiological Trends of Rheumatoid Arthritis and PADI4, PTPN22, and HLA-DRB9 Genes Distribution in the Kazakhstan Population

Abstract

BACKGROUND: The prevalence of rheumatoid arthritis (RA) is 1% in the global population. The lack of epidemiological studies in developing countries makes it difficult to obtain a complete global epidemiological picture of RA. RA develops due to the interaction of multiple genetic and environmental factors, though the contribution of these factors to the various disease occurrence seen in different populations is unclear. AIM: The aim of our study was to analyze the dynamics of the general prevalence and incidence of RA among the population of Kazakhstan in 2017–2019 as well as to investigate the three most common single-nucleotide polymorphisms (SNP) of RA in the Kazakhstan population. METHODS: The analysis of statistical data on Form 12 “On the health of the people and the health care system” was carried out. Prevalence and incidence rates were calculated according to generally accepted rules. Demographic data for the Republic of Kazakhstan were obtained from the official website stat.gov.kz. Our study included 70 RA patients and 113 control subjects. Blood samples were collected and genotyped for peptidylarginine deiminase 4 (PADI4), protein tyrosine phosphatase 22, and human leukocyte antigen (HLA)-DRB9 SNPs by reverse transcription polymerase chain reaction. RESULTS: The prevalence of RA in Kazakhstan in 2017–2019 was 0.36–0.38%, with an incidence rate of 0.085–0.087%, which can be comparable to data of other countries in Central Asia. The allele and genotypes frequency analyses were carried out between patients and controls. The HLA-DRB9 showed significant association of the G allele odds ratio (OR) 1.96 (95% confidence interval [CI]: 1.252–3.081), p= 0.0025 and G/G genotype OR = 3.67 (95% CI: 1.58–8.54), p = 0.00162 with RA in our sample. Strong association between anti-citrullinated protein antibody (ACPA) profile and PADI4 (OR 12.19 [95% CI: 2.19–67.94], p = 0.00115) was found. CONCLUSION: There was an increase in RA prevalence with age among females and a higher crude prevalence and incidence of RA in the southern regions of Kazakhstan. HLA-DRB9 prevailed in Kazakhstani patients with RA, PADI4 showed association with ACPA-positive RA. Further studies on larger samples are required to confirm our obtained results.