Determination of microbiomic and genomic biomarkers of rheumatoid arthritis in the kazakh population

"DETERMINATION OF MICROBIOMIC AND GENOMIC BIOMARKERS OF RHEUMATOID ARTHRITIS IN THE KAZAKH POPULATION"

IRN AR08052703

Implementation period: 2020-2022

 

Relevance: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disease that causes symmetrical erosive polyarthritis of both small and large joints, as well as characterized by damage to various internal organs and systems. The frequency of RA is 1% in the global population. The disease develops 3-5 times more often among women aged 30-60 years . In the absence of timely diagnosis and treatment, this disease in 40-70% of cases leads to disability in working age, as well as to death as a result of extra-articular lesions and complications. Currently, the relationship between external and internal risk factors in the development of this disease has been proven. Much attention in science today is paid to the leading endogenous factors, namely, microbiome and genetic predisposition. It is known, that the gastrointestinal tract harbors the largest human microbiome. One of the other areas with microbial populations, which is believed to significantly affect the human immune system, is the oral cavity, which contains more than 700 species of bacteria, the species diversity of which practically does not differ from the intestinal tract. Genome-wide studies (GWAS) have led to the discovery of more than 100 loci of genetic biomarkers of the main histocompatibility complex (MHC ) and beyond the MHC. Thus, non-receptor tyrosine phosphatase type 22 (protein tyrosine phosphatase, non-receptor type 22- PTPN22) has been identified as the most statistically significant biomarker for RA outside of MHC in populations of European origin. PADI4 (peptidyl-arginine deiminase type 4) has been shown to have an important association with RA in Asian populations. SNPs of other genes outside of MHC such as CD40, BLK, CTLA 4,PTPRC are also studied… Modern research methods, such as 16SRNA and RT PCR sequencing, as well as GWAS data, make it possible to widely study the influence of these factors on the development of RA and thereby expand the understanding of etiopathogenesis and improve the timely diagnosis of this disease. This project is a continuation of the state policy on the need to strengthen the health of the nation, which was voiced in the speeches of the first President of the Republic of Kazakhstan N.A.Nazarbayev and in the policy documents of the state. The expected results of the study will help identify new biomarkers of the disease by examining the oral microbiome and conducting SNP analysis. Prognostically significant results will be an improvement in the patient's quality of life - a decrease in disability, an increase in the level of socialization and social activity of patients with RA. The implementation of the study will make it possible to develop a methodology for identifying a risk group.

The object of the study is women in age of 30-55 years suffering from rheumatoid arthritis.

The aim of the work is to study new biomarkers of rheumatoid arthritis based on the study of oral microbiocenosis and SNP analysis, the intermediate goal is to study the features of the clinical course of RA among women.

The scope of application of the results: practical healthcare, rheumatologists, internists and general practitioners.

Expected results: To identify biomarkers of the disease by examining the microbiome of the oral cavity and conducting SNP analysis.

Achieved results:

  • Recruitment of the main (82 people) and control (118 people) study groups was carried out.
  • Sampling of the study material in the form of saliva and blood from all participants of the study was carried out.
  • DNA was isolated from the samples.
  • Bioinformatic analysis of the oral microbiome was carried out. As a result, statistically significant differences between the main and control groups were revealed, based on the study of α and β -diversity at the OTU level. As a result of the taxonomic identification of the bacterial community, the bacteria that dominated the main group were identified: Prevotella, Leptotrichia, Prevotella, Neisseria, Porphyrominas, Veillionella, Granulicatella, Campylobacter, TM7x. While the control group was dominated by Kingella, Selenomonas, F0332, Phyllobacterium, Sphingomonas.
  • An SNP analysis was carried out, which revealed a statistically significant predominance of HLA-DRB9 rs9268839 in the main group in comparison with the control group of the study on codominant, recessive and log-aditive inheritance models. When stratified by the form of RA, it was found that SYNGR1 rs909685 prevailed in patients with seropositive form of RA, while PADI4 rs2240340 and CTLA4.rs3087243 prevailed in ACPA-positive patients with RA. The nucleotide TAGAP.rs2451258 was also detected, which prevailed in ACPA-negative patients with RA.

 

Members of the research group:

Name

Participation in the project

Academic/academic degree

ORCID

Scopus Authors ID

Researcher ID

Assel Meiramova

Head

PhD

0000-0002-4030-0783

57203120043

ABF-2449-2021

Samat Kozhakhmetov

Implementer

Candidate of Biological Sciences,  Associate Professor

0000-0001-9668-0327

57223210171

N-4128-2017

Laura Chulenbayeva

Implementer

PhD

0000-0002-8691-9485

57205369003

ABE-9582-2021

Zhanar Akhmetova

Implementer

Candidate of Medical Sciences

0000-0001-9220-5596

57200608966

Q-5374-2018

Ayaulym Nurgozhina

 

Implementer

Master of Science

0000-0001-7042-4763

57207769556

-

Madiyar Nurgaziev

Implementer

Master of Biology

0000-0003-2397-4978

57216501021

AAV-9220-2020

Argul Issilbayeva

Implementer

Master of Medicine

0000-0002-7350-6083

57218655114

-