title: Genetic variation in C-reactive protein (CRP) gene may be associated with risk of systemic lupus erythematosus and CRP concentrations.
abstract: OBJECTIVE
  The gene coding for C-reactive protein (CRP) is located on chromosome 1q23.2, which falls within a linkage region thought to harbor a systemic lupus erythematosus (SLE) susceptibility gene. Recently, 2 single-nucleotide polymorphisms (SNP) in the CRP gene (+838, +2043) have been shown to be associated with CRP concentrations and/or SLE risk in a British family-based cohort. Our study was done to confirm the reported association in an independent population-based case-control cohort, and also to investigate the influence of 3 additional CRP tagSNP (-861, -390, +90) on SLE risk and serum CRP concentrations.
  
  
  METHODS
  DNA from 337 Caucasian women who met the American College of Rheumatology criteria for definite (n = 324) or probable (n = 13) SLE and 448 Caucasian healthy female controls was genotyped for 5 CRP tagSNP (-861, -390, +90, +838, +2043). Genotyping was performed using restriction fragment length polymorphism-polymerase chain reaction, pyrosequencing, or TaqMan assays. Serum CRP levels were measured using ELISA. Association studies were performed using the chi-squared distribution, Z-test, Fisher's exact test, and analysis of variance. Haplotype analysis was performed using EH software and the haplo.stats package in R 2.1.2.
  
  
  RESULTS
  While none of the SNP were found to be associated with SLE risk individually, there was an association with the 5 SNP haplotypes (p < 0.001). Three SNP (-861, -390, +90) were found to significantly influence serum CRP level in SLE cases, both independently and as haplotypes.
  
  
  CONCLUSIONS
  Our data suggest that unique haplotype combinations in the CRP gene may modify the risk of developing SLE and influence circulating CRP levels.
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: P Betty
authors.initials: PB
authors.lastname: Shih
authors.forename: Susan
authors.initials: S
authors.lastname: Manzi
authors.forename: Penny
authors.initials: P
authors.lastname: Shaw
authors.forename: Margaret
authors.initials: M
authors.lastname: Kenney
authors.forename: Amy H
authors.initials: AH
authors.lastname: Kao
authors.forename: Franklin
authors.initials: F
authors.lastname: Bontempo
authors.forename: M Michael
authors.initials: MM
authors.lastname: Barmada
authors.forename: Candace
authors.initials: C
authors.lastname: Kammerer
authors.forename: M Ilyas
authors.initials: MI
authors.lastname: Kamboh
mesh_terms: D000328:Adult; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors
chemical_list: D002097:C-Reactive Protein
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