Genetic variation in the CRP promoter: association with systemic lupus erythematosus.
The pentraxin C-reactive protein (CRP), an innate immune system opsonin which binds nuclear debris and apoptotic bodies, may protect against autoimmunity. A relative deficiency of CRP levels in patients with systemic lupus erythematosus (SLE) might contribute to altered handling of self-antigens. We report that the proximal 5' promoter region of CRP contains several polymorphisms that exhibit association with SLE in multiple populations. Strongest association was observed at the proximal promoter single nucleotide polymorphism (SNP) rs3093061 (CRP-707) (P = 6.41 x 10(-7) and P = 2.13 x 10(-6) in African-American and Caucasian case-control samples respectively). This association remains after adjustment for admixture. Linkage disequilibrium exists between SNPs in the proximal promoter and association of functional haplotypes containing rs3091244/rs3093062 (CRP-409/-390) appear to be driven by the rs3093061 (CRP-707) association. These data demonstrate that rs3093061 at the -707 site within the CRP gene is an SLE susceptibility locus.
Edberg
Jeffrey C
JC
Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294-2182, USA. jedberg@uab.edu
Wu
Jianming
J
Langefeld
Carl D
CD
Brown
Elizabeth E
EE
Marion
Miranda C
MC
McGwin
Gerald
G
Petri
Michelle
M
Ramsey-Goldman
Rosalind
R
Reveille
John D
JD
Frank
Summer G
SG
Kaufman
Kenneth M
KM
Harley
John B
JB
Alarcón
Graciela S
GS
Kimberly
Robert P
RP
D000328:Adult; D002097:C-Reactive Protein / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
D002097:C-Reactive Protein