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


METHODS
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).


CONCLUSIONS
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.
Hung
Adriana M
AM
Vanderbilt University Medical Center, 1161 21st Avenue South & Garland, Division of Nephrology, S-3223 MCN, Nashville, TN 37232-2372, USA. Adriana.hung@vanderbilt.edu
Crawford
Dana C
DC
Griffin
Marie R
MR
Brown-Gentry
Kristin
K
Lipkowitz
Michael S
MS
Siew
Edward D
ED
Cavanaugh
Kerri
K
Lewis
Julia B
JB
Ikizler
T Alp
TA
D001741:Black or African American; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000235:genetics*; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies
D000806:Angiotensin-Converting Enzyme Inhibitors; D002097:C-Reactive Protein