CRP polymorphisms and progression of chronic kidney disease in African Americans.

Hung AM, Crawford DC, Griffin MR, Brown-Gentry K, Lipkowitz MS, Siew ED, Cavanaugh K, Lewis JB, Ikizler TA, AASK Study Group
Clin J Am Soc Nephrol. 2010 5 (1): 24-33

PMID: 19965533 · PMCID: PMC2801650 · DOI:10.2215/CJN.01900309

BACKGROUND AND OBJECTIVES - Chronic inflammation may play a role in chronic kidney disease (CKD) progression. CRP gene polymorphisms are associated with serum C-reactive protein (CRP) concentrations. It is unknown if CRP polymorphisms are associated with CKD progression or modify the effectiveness of anti-hypertensive therapy in delaying CKD progression.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS - We genotyped 642 participants with CKD from the African American Study of Kidney Disease and Hypertension (AASK), selecting five tag polymorphisms: rs2808630, rs1205, rs3093066, rs1417938, and rs3093058. We compared the minor allele frequencies (MAF) of single nucleotide polymorphisms (SNPs) in AASK to MAFs of African Americans from NHANES III. Among AASK participants, we evaluated the association of SNPs with CRP levels and prospectively with a composite: halving the GFR, ESRD, or death.

RESULTS - The MAF was higher for the rs2808630_G allele (P = 0.03) and lower for the rs1205_A allele (P = 0.03) in the AASK compared with NHANES III. Among AASK participants, the rs3093058_T allele predicted higher CRP concentrations (P < 0.0001) but not CKD progression. The rs2808630_GG genotype was associated with higher risk of the composite endpoint compared with the AA genotype (P = 0.002). Participants with the rs2808630_GG genotype on angiotensin converting enzyme inhibitors (ACEIs) versus beta blockers had increased risk of progression (P = 0.03).

CONCLUSION - CRP SNPs that were associated with higher levels of CRP did not predict CKD progression. The rs2808630_GG genotype was associated with higher risk of CKD progression, and in patients with this genotype, ACEIs did not slow progression.

MeSH Terms (12)

African Americans Angiotensin-Converting Enzyme Inhibitors C-Reactive Protein Chronic Disease Disease Progression Female Humans Kidney Diseases Male Middle Aged Polymorphism, Genetic Prospective Studies

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