by Raja Chinthamuneedi
Tutor: Karen Young
Tutor: Karen Young
Hey everyone, I recently came across this interesting article on Rheumatoid Arthritis (RA), published in 2010 by Soumya Raychaudhuri. RA is a complex, autoimmune disease in which the body’s immune system attacks the soft tissue membrane that lines its own joints (figure to the left). RA causes chronic inflammation in joints as well as in other tissues and thus organs around the body and in recent years a causal relationship has been formed between genetic risk factors involved with the disease, such as the sharing of particular alleles.
Since 2008 there have been great genetic advances in RA’s understanding as genotypic studies have determined a number of risk loci and their pathways in RA. I was so intrigued by this article that I thought I would review and share recent research and genetic advances in the study of RA.
The development in genetic technologies and strategies have allowed for an increase in the number of risk loci detected in the genetic makeup of a RA carrying organism. Raychaudhuri indicated that the two main strategies that have been used effectively to ascertain risk loci in RA are Single Nucleotide Polymorphism (SNP) studies and unbiased Genome-Wide Association Studies (GWASs).
The first main strategy is SNP studies, which investigate single nucleotide alterations within genes that have a probable association with the disease based on their genetics and functionality (figure right). Although changes in nucleotides are not necessarily the cause of the disease, it is probable that they are associated with the mutations responsible for causing the disease.
Alternatively, GWASs utilise SNP detecting technology in conjunction with data collected from numerous case-control studies, thus conducting a meta-analysis that allows associated alleles and loci to be promptly identified. Risk alleles can also be discovered effectively using the candidate SNP approach. This is a unique approach which studies individual SNPs and has found common SNP loci that may be predisposed to autoimmune diseases.
Using the techniques mentioned above, it was found that the greatest amount of genetic variation occurs in the HLA-DRB1 risk alleles located in the Major Histocompatibility Complex (MHC) region in chromosome 6 (picture below). These shared epitope alleles are predicted to contribute to approximately 18 to 37% of the total genetic variability of RA (van der Woude et al. 2009; Deighton et al. 1989). Due to the intricacy of the MHC region, the effectiveness of current strategies and approaches is greatly reduced. However, due to its importance, as more technological and strategic developments transpire, scientists will attempt to identify risk alleles present in the MHC region.
Additional studies have suggested that amongst several RA risk loci, there are common pathways through which the disease can develop (Raychaudhuri, S 2010); however, the high degree of specificity required for the clinical applicability of these studies has not yet been reached. Although, current research can offer an understanding into the risk of RA for people within certain populations, future progress in the field of genetic studies will broaden current knowledge on RA and its causes.
In summary, in recent years advances in the field of genetics have helped develop a current understanding of RA and have aided in the discovery of risk variants. The discovery of risk loci and the pathways they implicate allows for the analysis of potential immunological processes involved in the disease’s pathogenesis. Although there have been many advances in RA research to date, future developments will greatly expand current knowledge regarding the genetics underpinning RA.
I hope you all found this article as interesting as I did and can see the vast future possibilities that studies of the ilk have on the treatment of autoimmune diseases such as RA.