Different genome-wide linkage and association studies performed during the last 15 years have associated mutations and polymorphisms in complement genes with different diseases characterized by tissue damage and inflammation. These are complex disorders in which genetically susceptible individuals usually develop the pathology as a consequence of environmental triggers. Although complement dysregulation is a common feature of these pathologies, how the disease phenotype is determined is only partly understood. One way to advance understanding is to focus the research in the analysis of the peculiar genotype-phenotype correlations that characterize some of these diseases. I will review here how understanding the functional consequences of these disease-associated complement genetic variants is providing us with novel insights into the underpinning complement biology and a better knowledge of the pathogenic mechanisms underlying each of these pathologies. These advances have important therapeutic and diagnostic implications.
Keywords: C3; CFHRs; Complement; Disease susceptibility; Factor H; Factor H-related proteins.
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