Abstract
BackgroundSerum amyloid A (SAA) is secreted by liver hepatocytes in response to increased inflammation whereupon it associates with high-density lipoprotein (HDL) and alters the protein and lipid composition of HDL negating some of its anti-atherogenic properties.AimsTo identify variants within the SAA gene that may be associated with SAA levels and/or cardiovascular disease (CVD).MethodsWe identified exonic variants within the SAA genes by deoxyribonucleic acid (DNA) Sanger sequencing. We tested the association between SAA variants and serum SAA levels in 246 individuals with and without CVD.ResultsIncreased SAA was associated with rs2468844 (beta [β] = 1.73; confidence intervals [CI], 1.14–1.75; p = 0.01), rs1136747 (β = 1.53 (CI, 1.11–1.73); p = 0.01) and rs149926073 (β = 3.37 (CI, 1.70–4.00); p = 0.02), while rs1136745 was significantly associated with decreased SAA levels (β = 0.70 (CI, 0.53–0.94); p = 0.02). Homozygous individuals with the SAA1.3 haplotype had significantly lower levels of SAA compared with those with SAA1.1 or SAA1.5 (β = 0.43 (CI, 0.22–0.85); p = 0.02) while SAA1.3/1.5 heterozygotes had significantly higher SAA levels compared with those homozygous for SAA1.1 (β = 2.58 (CI, 1.19–5.57); p = 0.02).ConclusionsWe have identified novel genetic variants in the SAA genes associated with SAA levels, a biomarker of inflammation and chronic disease. The utility of SAA as a biomarker for inflammation and chronic disease may be influenced by underlying genetic variation in baseline levels.
Highlights
Chronic diseases such as diabetes mellitus and cardiovascular disease (CVD) are increasing global health concerns [1, 2] thatElectronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Serum amyloid A (SAA) protein concentrations increase up to 1000-fold in response to infection, injury and inflammation [5,6,7,8]
A total of 252 participants were recruited to the study; serum and deoxyribonucleic acid (DNA) samples were only available for 246 participants; these were split into two categories, no CVD (n = 100) and CVD (n = 146) (Table 1)
No single nucleotide polymorphisms (SNPs) with a minor allele frequency (MAF) > 5% were identified in SAA1 exon 2, SAA2 exons 1, 2, and 3 or any exons of SAA4
Summary
Serum amyloid A (SAA) protein concentrations increase up to 1000-fold in response to infection, injury and inflammation [5,6,7,8]. There is increasing evidence that implicates SAA in the pathological processes of multiple chronic diseases [12]. SAA readily associates with high-density lipoprotein (HDL), becoming the major carrier of this protein in the circulation [13, 14]. A (SAA) is secreted by liver hepatocytes in response to increased inflammation whereupon it associates with high-density lipoprotein (HDL) and alters the protein and lipid composition of HDL negating some of its antiatherogenic properties. Aims To identify variants within the SAA gene that may be associated with SAA levels and/or cardiovascular disease (CVD). We tested the association between SAA variants and serum SAA levels in 246 individuals with and without CVD
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