DRAGoN stands for “Deciphering Diversities: Renal Asian Genetics Network”. It is a research consortium based in National University of Singapore, set up to investigate glomerular and proteinuric diseases in Asians. The network consists of nephrologists, paediatricians, pathologists scientists and biostatisticians.
Why is DRAGoN set up?
Primary glomerular disease, including focal segmental glomerulosclerosis (FSGS), is a common cause of renal failure in adults and children worldwide. Current treatment strategies are largely empirical and involve the use of immunosuppressive drugs which are often non-targeted, toxic and expensive. Yet, response rates are not always desirable. To date, more than 50 genes are known to cause proteinuric or familial haematuric diseases. Many of these are traditionally monogenic diseases. However, with next generating sequencing, we are entering a new paradigm as our understanding of these diseases are being challenged, and the workup of difficult childhood nephrotic syndrome now includes genetic evaluation.
Unlike Europe and North America where large consortiums exist, the genetics of renal diseases in Asia is largely understudied. Because of the relative rare nature of the diseases, systematic evaluation is best achieved with a large multicenter, multinational consortium. There has been evidence that the genetic causes of glomerular diseases in Asia differ from other parts of the world. For example, Asian children with sporadic steroid-resistant nephrotic syndrome have a much lower prevalence of podocin mutations compared to Caucasian and Middle East patients. Moreover, the Malay race appears to have a higher predisposition towards renal disease compared to other Asian races. This phenomenon is strikingly similar to the higher incidence of FSGS and renal impairment in African Americans, in whom MYH9 and APOL1 have been recognized as significant risk alleles.
Autosomal recessive polycystic kidney disease (ARPKD) and nephronophthisis-related ciliopathies (NPHP-RC) have in common genetic basis involving proteins that are critical in the structure/function of the primary apical cilium, and are now known together as the hepatorenal fibrocystic kidney diseases (HRFD).
There has been recent evidence suggesting that there may be as yet undiscovered pathogenic genes underlying the HRFD phenotype amongst the families in Asia. In addition, a precise genetic diagnosis has important implications for prognostication, as well as family planning and planning for a renal transplant.
Identification of genetic basis of HRFD in Asia will allow for estimation of lifetime risks for kidney disease, as well as genetic risk stratification for disease course and response to therapy.
Our mission is to advance our understanding of the demographics, genetics and clinical features of primary glomerular diseases and cystic diseases in Asians. We aim to provide the basis to direct future functional work, so as to improve clinical management strategies and explore innovative treatment targets for glomerular diseases.