CRP polymorphisms and progression of chronic kidney disease in African Americans

Area of Science:

• Genetics and Molecular Biology
• Nephrology
• Cardiovascular Research

Background:

• Chronic inflammation is implicated in chronic kidney disease (CKD) progression.
• C-reactive protein (CRP) gene polymorphisms influence serum CRP levels.
• The association between CRP gene variants and CKD progression, or their impact on antihypertensive therapy, remains unclear.

Purpose of the Study:

• To investigate the association between CRP gene polymorphisms and CKD progression.
• To determine if CRP gene polymorphisms modify the effectiveness of antihypertensive treatments in slowing CKD progression.

Main Methods:

• Genotyping of 642 participants with CKD from the African American Study of Kidney Disease and Hypertension (AASK) for five tag single nucleotide polymorphisms (SNPs) in the CRP gene.
• Comparison of minor allele frequencies (MAFs) in AASK participants with those from NHANES III.
• Evaluation of the association of SNPs with serum CRP levels and a composite endpoint of halved GFR, end-stage renal disease (ESRD), or death.

Main Results:

• The rs2808630_G allele and rs1205_A allele showed different MAFs in AASK compared to NHANES III.
• The rs3093058_T allele was associated with higher CRP levels but not CKD progression.
• The rs2808630_GG genotype was linked to a higher risk of the composite endpoint (P = 0.002).
• In participants with the rs2808630_GG genotype, angiotensin-converting enzyme inhibitors (ACEIs) were associated with an increased risk of progression compared to beta-blockers (P = 0.03).

Conclusions:

• CRP SNPs associated with elevated CRP levels did not predict CKD progression.
• The rs2808630_GG genotype is associated with an increased risk of CKD progression.
• For individuals with the rs2808630_GG genotype, ACEIs did not demonstrate a benefit in slowing CKD progression.