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

Clin Endocrinol (Oxf). 2013 Oct;79(4):504-9. doi: 10.1111/cen.12078. Epub 2013 Apr 6.

Abstract

Objective: 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).

Methods: 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.

Results: 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenomedullin / blood*
  • Adult
  • Asian People / genetics
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / ethnology
  • Cardiovascular Diseases / genetics
  • Female
  • Gene Frequency
  • Genotype
  • Haplotypes
  • Hong Kong / epidemiology
  • Humans
  • Interleukin-6 / genetics*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polymorphism, Single Nucleotide*
  • Prevalence
  • Risk Factors
  • Sex Factors

Substances

  • Interleukin-6
  • Adrenomedullin