A SNP in the 5’ flanking region of the SAA1 gene is associated with serum levels of serum amyloid A and cardiovascular risk factors

Abstract

Abstract Background Elevated serum levels of serum amyloid A (SAA) are associated with increased risk of cardiovascular disease. In this study, we examine associations between allelic variation in the rs11024595 single nucleotide polymorphism (SNP) in the 5’ flanking region of the SAA1 gene and adipose tissue gene expression, serum levels of SAA and cardiovascular risk factors. Methods DNA samples from 729 participants in the SibPair study, comprising weight discordant siblings and their biological parents, and 3542 participants (1783 patients treated with bariatric surgery and 1759 controls) from the Swedish Obese Subjects (SOS) study were used. The rs11024595 SNP was genotyped in both cohorts using Pyrosequencing or the Sequenom MassARRAY platform, respectively. Blood chemistry and anthropometry were assessed at study start. Adipose tissue SAA1 gene expression and serum levels of SAA in the SibPair study were analyzed with DNA microarray or immunoassay, respectively. Results In the SibPair study, the rs11024595 SNP was associated with serum levels of SAA (P = 0.0050) where T allele carriers displayed lower levels of SAA (P = 0.0025) but no association between genotype and adipose tissue SAA1 gene expression was found. In the SOS study, the rs11024595 SNP was associated with serum levels of HDL cholesterol (P = 0.0045), triglycerides (P = 0.025) and apolipoprotein E (P = 0.026). Moreover, T allele carriers had lower levels of HDL cholesterol (P = 0.0148), but higher levels of triglycerides (P = 0.0418) and apolipoprotein E (P = 0.028) compared to C allele homozygotes. The rs11024595 SNP was also associated with plasma glucose (P = 0.044). Conclusions The rs11024595 SNP in the 5’ flanking region of the SAA1 gene is associated with both serum levels of SAA and other cardiovascular risk factors. Future studies are required to elucidate whether the rs11024595 SNP can affect the risk of cardiovascular events. Trial registration ClinicalTrials.gov Identifier: NCT01479452 Registered 24 November 2011 - retrospectively registered.