title: IL-6 gene variation is associated with IL-6 and C-reactive protein levels but not cardiovascular outcomes in the Cardiovascular Health Study.
abstract: Interleukin-6 (IL-6) and C-reactive protein (CRP) levels increase with age and likely play a role in adverse health outcomes in older adults. The relationship between IL-6 gene tag single nucleotide polymorphisms (SNPs) and circulating IL-6 and CRP levels, cardiovascular disease (CVD) outcomes, and mortality in Caucasian (CA) and African American (AA) participants of the Cardiovascular Health Study (CHS) was evaluated using ANCOVA and Cox proportional hazards models. The minor allele of the promoter SNP 1510 and intronic SNP 3572 associates with significantly higher serum IL-6 and CRP levels in CA but not AA. The CRP association persisted after CA and AA populations were combined and after accounting for multiple comparisons. These associations did not carry through to cardiovascular disease outcomes. Decreased risk of stroke was identified in CA, with the minor allele of SNP 1111 (HRR 0.71, 95% CI 0.52, 0.95), P = 0.02, and increased risk of CVD and all-cause mortality (HRR 1.31, 95% CI 1.05-1.64) in AAs heterozygote for SNP 2989. While genetic variation in the IL-6 gene was associated with circulating IL-6 and especially with CRP concentrations in this study, there is little evidence for association between common IL-6 gene variation and adverse health outcomes in this population of older adults.
authors.affiliation: Johns Hopkins Medical Institutions, Johns Hopkins University, John R Burton Pavilion, 5505 Hopkins Bayview Circle, Baltimore, MD 21224, USA. jwalston@jhmi.edu
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Walston
authors.forename: M Daniele
authors.initials: MD
authors.lastname: Fallin
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.forename: Leslie
authors.initials: L
authors.lastname: Lange
authors.forename: Bruce
authors.initials: B
authors.lastname: Psaty
authors.forename: Nancy
authors.initials: N
authors.lastname: Jenny
authors.forename: Warren
authors.initials: W
authors.lastname: Browner
authors.forename: Russell
authors.initials: R
authors.lastname: Tracy
authors.forename: Peter
authors.initials: P
authors.lastname: Durda
authors.forename: Alex
authors.initials: A
authors.lastname: Reiner
mesh_terms: D001741:Black or African American / Q000235:genetics; D000368:Aged; D000483:Alleles; D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics*; D007438:Introns; D008137:Longitudinal Studies; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D044465:White People / Q000235:genetics
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D002097:C-Reactive Protein