Identification of rheumatoid arthritis biomarkers based on single nucleotide polymorphisms and haplotype blocks: A systematic review and meta-analysis

Abstract

Genetics of autoimmune diseases represent a growing domain with surpassing biomarker results with rapid progress. The exact cause of Rheumatoid Arthritis (RA) is unknown, but it is thought to have both a genetic and an environmental bases. Genetic biomarkers are capable of changing the supervision of RA by allowing not only the detection of susceptible individuals, but also early diagnosis, evaluation of disease severity, selection of therapy, and monitoring of response to therapy. This review is concerned with not only the genetic biomarkers of RA but also the methods of identifying them. Many of the identified genetic biomarkers of RA were identified in populations of European and Asian ancestries. The study of additional human populations may yield novel results. Most of the researchers in the field of identifying RA biomarkers use single nucleotide polymorphism (SNP) approaches to express the significance of their results. Although, haplotype block methods are expected to play a complementary role in the future of that field.

Keywords: Haplotype block; Linkage disequilibrium; Major histocompatibility complex; Rheumatoid arthritis; Single nucleotide polymorphism.

Graphical abstract

Fig. 1

More than 35 risk loci that have been previously identified as biomarkers for RA disease .

Fig. 2

The MHC region showing class I, class II, and class III regions .

Fig. 3

LD structure for 12 SNPs at HLA–DRB1 and HLA–DPB1. A constructed block was shown including eight SNPs, from SNP 5 to SNP 12 .

Fig. 4

Case-control association results at 6q23. The associated SNP (rs10499194) was about 165 kb from both TNFAIP3 and OLIG3 genes .

Fig. 5

Manhattan plots of the GWAS meta-analysis for RA in the Japanese population .

Fig. 6

Manhattan plot of association with RA in the European descents .