title: Single-nucleotide polymorphisms at five loci are associated with C-reactive protein levels in a cohort of Filipino young adults.
abstract: C-reactive protein (CRP) is a component of nonspecific immune defense and is a reliable marker of low-grade inflammation involved in obesity, type 2 diabetes and cardiovascular disease. Genome-wide association studies in middle-aged and elderly populations, predominantly of European descent, demonstrated associations of CRP levels with single-nucleotide polymorphisms (SNPs) at several loci. To examine whether the variants identified are replicated in Filipino young adults, we applied Tobit regression models to study the association of plasma CRP with 12 SNPs at seven loci in a cohort of 1691 Filipino young adults (aged 21.5±0.3 years) from the Cebu Longitudinal Health and Nutrition Survey. SNPs in or near CRP (P=3.2 × 10(-11)), HNF1A, IL6R, APOE-APOC1 and LEPR showed significant associations (P<0.05) and together explained 4.8% of the total variation in CRP. Modest interactions were observed between LEPR-rs1892534 and waist circumference (uncorrected P(interaction)=0.020) and between APOE-rs769449 and pathogen exposure (uncorrected P(interaction)=0.0073) in models predicting CRP. Our results demonstrated that variants in several loci are significantly associated with plasma CRP in Filipino young adults, suggesting shared genetic influences on circulating CRP across populations and age groups.
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, NC 27599-7264, USA.
authors.forename: Ghenadie
authors.initials: G
authors.lastname: Curocichin
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.forename: Thomas W
authors.initials: TW
authors.lastname: McDade
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Kuzawa
authors.forename: Judith B
authors.initials: JB
authors.lastname: Borja
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Lange
authors.forename: Linda S
authors.initials: LS
authors.lastname: Adair
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Lange
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mohlke
mesh_terms: D000293:Adolescent; D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics; D044466:Asian People / Q000235:genetics; D002097:C-Reactive Protein / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D008297:Male; D010679:Philippines; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D001057:Apolipoproteins E; D002097:C-Reactive Protein