Complement factor H polymorphisms, renal phenotypes and age-related macular degeneration: the Blue Mountains Eye...

Area of Science:

• Genetics
• Nephrology
• Ophthalmology

Background:

• Complement factor H (CFH) regulates the alternative complement pathway.
• CFH mutations are linked to kidney diseases (MPGN II, aHUS) and age-related macular degeneration (AMD).
• Dysregulation of the alternative pathway may underlie these ocular and renal conditions.

Purpose of the Study:

• To investigate the role of common CFH variants in renal function within the Australian population.
• To confirm associations between CFH variants and kidney function and AMD in the Blue Mountains Eye Study (BMES).

Main Methods:

• Genotyping of CFH variants I62V and Y402H in the BMES cohort.
• Statistical analysis to assess the association of these variants with estimated glomerular filtration rate (GFR), creatinine clearance (CRCL), and AMD status.

Main Results:

• The I62V variant was significantly associated with reduced GFR and CRCL (P=0.017 and P=0.015, respectively). Each copy of the minor allele (G) decreased GFR/CRCL by approximately 0.98 ml/min/1.73 m(2).
• The Y402H variant was confirmed to be associated with AMD. The minor allele (C) increased the odds of AMD (OR=1.87 for CC vs TT).
• The population attributable risk (PAR) for the Y402H C allele was estimated at 0.22 (95% CI: 0.15, 0.28).

Conclusions:

• Common CFH variants, specifically I62V and Y402H, play a significant role in renal function and AMD susceptibility in the Australian population.
• The findings reinforce the link between alternative complement pathway dysregulation and both ocular and renal diseases.
• I62V impacts kidney function, while Y402H is a risk factor for AMD, highlighting CFH's broad clinical relevance.