LAUSR

BACKGROUND Thrombotic microangiopathy (TMA) occurs in immunoglobulin A nephropathy (IgAN), and the pathogenesis is not known behind the endothelium injury. The genetic studies have indicated that complement factor H (CFH) and complement factor H-related protein genes (CFHRs)play a key role in IgAN. We perform a study to investigate the CFH /CFHRs gene variants and their roles in IgAN with microangiopathy based on a previous genome-wide association study (GWAS). METHODS We re-review microangiopathic lesions in 2055 IgAN patients by light microscopy. And 204 IgAN patients with MA and 1851 IgAN without MA are confirmed in this study. Nineteen single nucleotide polymorphisms (SNPs) across CFH and CFHRs genes information are extracted from GWAS data. RESULTS The results show that 204 out of 2055(9.93 %) MA patients are screened from our IgAN cohort. Patients with MA lesions are strongly associated with more severe clinical conditions and higher serum complement factor H (FH) levels than IgAN without MA(MA vs IgAN-non MA:428.16 ± 141.05 vs 364.62 ± 139.06ug/mL, p = 0.004). The genetic association study indicates the frequency of rs800292-G in CFH was significantly higher in the MA group (0.441 vs 0.374, odds ratio1.37[1.07-1.62], p = 0.010) compared with IgAN without MA. In addition, patients with the rs412852-G allele in CFH become an independent risk factor for end-stage renal disease (ESRD)in MA patients (Hazard Ratio 2.77[1.17-6.65], p = 0.021). However, the gene variants did not correlate with serum FH, serum C3, and C3 deposits in the renal specimens. CONCLUSION Our results indicated that variants in CFH are associated with the development and progression of IgAN with microangiopathy.