A single nucleotide polymorphism of interleukin-6 gene is related to plasma adrenomedullin levels

Abstract

OBJECTIVE: Plasma adrenomedullin (ADM) level is elevated in inflammation and is associated with cardiovascular diseases. Single nucleotide polymorphisms (SNPs) in the ADM gene have been found to be associated with ADM level. The 5'-flanking region of ADM is known to contain a consensus sequence of the binding site for the nuclear factor for interleukin-6 (IL-6). Therefore, we investigated if plasma ADM level is related to SNPs in the IL6 gene. METHODS: Plasma ADM level was measured in 476 subjects (236 men, 240 women; mean age 50.9±10.8 years) in the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISP2). The subjects were genotyped for three tagging SNPs in the IL-6 gene. RESULTS: The minor allele frequencies of the IL-6 SNPs rs17147230, rs1800796 and rs2069837 were 41.8%, 20.0% and 15.4% respectively. The SNP rs17147230, was associated with plasma ADM level after adjusting for age and sex (β=-0.096, P=0.034). The association was significant in women (β=-0.115, P=0.021) but not in men. Amongst all subjects, plasma ADM level decreased with an increasing number of minor alleles of rs17147230 in multivariate analysis (P=0.034). Compared to subjects with AA genotype, subjects with TT genotype had a plasma ADM level 12.8% lower (95% CI: 0.6%-23.5%, P=0.041). CONCLUSION: Plasma ADM level is related to the SNP rs17147230 in IL-6 gene, and the association appears stronger in women. The effect of the polymorphism on inflammation and cardiovascular disease remains to be determined.