Genetic determinants of basal C-reactive protein expression in Filipino systemic lupus erythematosus families.
Basal C-reactive protein (CRP) is a heritable trait associated with long-term cardiovascular disease risk. Existing studies leave ambiguity over the key functional polymorphisms and fail to adjust for trans-acting effects. In a novel cohort of 285 Filipino systemic lupus erythematosus probands and their first-degree relatives, we quantified serum CRP and typed a dense map of CRP single-nucleotide polymorphisms (SNPs), along with SNPs in the interleukin-1 beta, interleukin-6 and apolipoprotein E genes. Ten CRP SNPs demonstrated association with basal CRP in a regression model (P=0.011-0.002). These delineated two haplotypes associated with high and low basal CRP expression (P=0.002). Differences in allele frequency were seen compared with Caucasian populations, enabling us to argue for an independent genetic effect from a phylogenetically distinct haplotype tagged by SNP rs1800947. We demonstrated an association between Apo epsilon 2 and higher basal CRP. Interleukin-6 genotype was associated with basal CRP, highlighting a role for acute-phase cytokines even in basal expression. Identifying these trans-acting variants may improve the use of basal CRP as a predictor cardiovascular risk, and increase our power to detect associations between CRP and disease.
Rhodes
B
B
Department of Rheumatology, Molecular Genetics and Rheumatology Section, Imperial College London, London, UK.
Wong
A
A
Navarra
S V
SV
Villamin
C
C
Vyse
T J
TJ
D000328:Adult; D000595:Amino Acid Sequence / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D002097:C-Reactive Protein / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010679:Philippines / Q000453:epidemiology; D012307:Risk Factors
D002097:C-Reactive Protein