HLA-DP REGION GENE POLYMORPHISM IN PRIMARY IGA NEPHROPATHY - NO ASSOCIATION

Many features suggest that a genetically mediated abnormally of the Ig A immune response is central in the pathogenesis of IgA nephropathy (I gAN). Candidate disease susceptibility genes include those encoding th e MHC class II antigens, HLA-DR, -DQ, and -DP, and we have recently de scribed an HLA-DQB1 association in IgAN. Polymorphisms of the HLA-DP r egion loci have been shown to associate with autoimmune diseases which share immunological features with IgAN; coeliac disease (CD) and derm atitis herpetiformis (DH). We have therefore examined restriction frag ment length polymorphisms (RFLPs) of the DP-alpha and DP-beta-chain ge nes (DPA1 and DPB1 respectively) in IgAN, and have studied three cauca soid populations (North, Mid, Southern Europe) to determine whether et hnic variation in genetic susceptibility exists. DNA was extracted fro m blood (IgAN, UK n = 89, Italy n = 75, Finland n = 49; Controls, UK n = 99, Italy n = 54, Finland n = 45), and studied by Southern blot hyb ridization techniques using the restriction enzymes BgI II and Msp I a nd cDNA P-32-labelled DPA1 and DPB1 probes respectively. The frequency distribution of the DPA1 and DPB1 fragments was similar between the t hree caucasoid IgAN patient groups compared to their respective contro ls. There was no association of DPA1 or DPB1 RFLPs with clinical featu res. These results suggest that HLA-DP region genes are not important in conferring disease susceptibility to IgAN and do not influence clin ical disease expression. Moreover, different immunogenetic mechanisms operate in IgAN, CD, and DH.