Plasma adrenomedullin level is related to plasma interleukin-6 and a polymorphism in the adrenomedullin gene

Abstract

INTRODUCTION: Adrenomedullin is involved in inflammation and like interleukin-6 (IL-6) and C-reactive protein (CRP), is a good biomarker of cardiovascular risk. Therefore, we studied common single nucleotide polymorphisms (SNPs) in the gene encoding adrenomedullin (ADM) and their relation with the plasma levels of adrenomedullin and other inflammatory markers. METHODS: Plasma adrenomedullin, IL-6 and CRP were measured in 476 subjects from the population-based Hong Kong Cardiovascular Risk Factor Prevalence Study-2. Four SNPs in ADM were genotyped. RESULTS: Plasma adrenomedullin decreased with age (beta = -0.089, P = 0.049). Each tertile of plasma adrenomedullin was associated with a plasma IL-6 level 11.9% (95% CI: 2.6–20.3%) lower (beta = -0.116, P = 0.014). Plasma adrenomedullin level was not related to other clinical characteristics, including plasma CRP, fibrinogen and adiponectin levels. The four SNPs, rs3814700, rs11042725, rs34354539 and rs4910118 had minor allele frequencies of 31.1%, 28.7%, 33.8% and 23.4% respectively. Carriers of the minor allele of rs4910118 had plasma adrenomedullin level 10.5% (95% CI: 2.5–17.8%) lower than the non-carriers (beta = -0.115, P = 0.011). Haplotype analysis revealed a similar significant association with plasma adrenomedullin (overall P = 0.040). CONCLUSIONS: Plasma adrenomedullin is related to IL-6 but not CRP, which is consistent with the ability of adrenomedullin to stimulate IL-6 production in vitro. Plasma adrenomedullin is also influenced by a common polymorphism, which means that including the genotype may improve cardiovascular risk prediction.