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

Abstract

Elevated plasma adrenomedullin (ADM) levels are associated with cardiovascular diseases. Single nucleotide polymorphisms (SNPs) in the gene encoding ADM (ADM) are associated with plasma ADM levels. The presence of a nuclear factor for interleukin-6 (IL-6) expression binding site in the promoter region of the ADM gene suggests a possible relationship between the expression of the ADM and IL-6. Therefore, we investigated whether plasma ADM levels are related to SNPs in the gene encoding IL-6 (IL6). Plasma ADM levels were measured in 476 subjects in the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS2). The subjects were genotyped for three tagging SNPs in the IL6 gene. The minor allele frequencies of the IL6 SNPs rs17147230, rs1800796 and rs2069837 were 41·8%, 20·0% and 15·4%, respectively. The tagging SNP, rs17147230, was associated with plasma ADM levels 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. Among all subjects, plasma ADM levels decreased with an increasing number of minor alleles of rs17147230 in multivariate analysis (P=0·034). Compared to subjects with the AA genotype, subjects with the TT genotype had plasma ADM levels 12·8% lower (95% CI: 0·6-23·5%, P=0·041). Haplotype analysis demonstrated a significant association of the haplotype ACA with plasma ADM levels in women (P<0·05). Plasma ADM levels are related to the SNP rs17147230 in IL6 gene. The effect of the polymorphism on inflammation and cardiovascular disease remains to be determined.