[show abstract][hide abstract] 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.
Journal of Human Genetics 09/2011; 56(12):823-7. · 2.37 Impact Factor
[show abstract][hide abstract] ABSTRACT: Adiponectin is an adipocyte-secreted protein involved in a variety of metabolic processes, including glucose regulation and fatty acid catabolism. We conducted a genome-wide association study to investigate the genetic loci associated with plasma adiponectin in 1776 unrelated Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS). Our strongest signal for adiponectin mapped to the gene CDH13 (rs3865188, P ≤ 7.2 × 10(-16)), which encodes a receptor for high-molecular-weight forms of adiponectin. Strong association was also detected near the ADIPOQ gene (rs864265, P = 3.8 × 10(-9)) and at a novel signal 100 kb upstream near KNG1 (rs11924390, P = 7.6 × 10(-7)). All three signals were also observed in 1774 young adult CLHNS offspring and in combined analysis including all 3550 mothers and offspring samples (all P ≤ 1.6 × 10(-9)). An uncommon haplotype of rs11924390 and rs864265 (haplotype frequency = 0.050) was strongly associated with lower adiponectin compared with the most common C-G haplotype in both CLHNS mothers (P = 1.8 × 10(-25)) and offspring (P = 8.7 × 10(-32)). Comprehensive imputation of 2653 SNPs in a 2 Mb region using as reference combined CHB, JPT and CEU haplotypes from the 1000 Genomes Project revealed no variants that perfectly tagged this haplotype. Our findings provide the first genome-wide significant evidence of association with plasma adiponectin at the CDH13 locus and identify a novel uncommon KNG1-ADIPOQ haplotype strongly associated with adiponectin levels in Filipinos.
Human Molecular Genetics 09/2010; 19(24):4955-64. · 7.69 Impact Factor