• Kayleigh Griffiths, Alexander P Maxwell, Rachel V McCarter, Patrick Nicol, Ruth E Hogg, Mark Harbinson, and Gareth J McKay.
• Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland.
• Ir J Med Sci. 2019 Nov 1; 188 (4): 1175-1183.

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.

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