Complement factor H variants are associated with microangiopathy lesions in IgA nephropathy

Area of Science:

• Nephrology
• Genetics
• Immunology

Background:

• Thrombotic microangiopathy (TMA) is a complication of immunoglobulin A nephropathy (IgAN), but its underlying endothelial injury mechanisms remain unclear.
• Genetic studies implicate complement factor H (CFH) and complement factor H-related protein (CFHR) genes in IgAN pathogenesis.

Purpose of the Study:

• To investigate the role of CFH/CFHR gene variants in IgAN patients who develop TMA.
• To analyze the association between specific genetic variations and clinical outcomes in IgAN with TMA.

Main Methods:

• Reviewed microangiopathic lesions in 2055 IgAN patients using light microscopy.
• Confirmed 204 IgAN patients with TMA and 1851 without TMA.
• Extracted genetic information on 19 single nucleotide polymorphisms (SNPs) across CFH and CFHRs genes from genome-wide association study (GWAS) data.

Main Results:

• TMA was identified in 9.93% of the IgAN cohort (204/2055 patients).
• MA patients exhibited more severe clinical conditions and higher serum complement factor H (FH) levels compared to IgAN patients without MA (p=0.004).
• The rs800292-G variant in CFH was significantly more frequent in the MA group (OR=1.37, p=0.010), and the rs412852-G allele was an independent risk factor for end-stage renal disease (ESRD) in MA patients (HR=2.77, p=0.021).

Conclusions:

• CFH gene variants are associated with the development of TMA in IgAN.
• These genetic variations contribute to the progression of IgAN with microangiopathy and increase the risk of ESRD.