Lipoproteins and Hyperlipoproteinemia: Links to Gout

Abstract

Gout and cardiovascular disease are both complex and multi-factorial with genetic predisposition and environmental triggers. Not only do both have high co-morbidity with other metabolic conditions, gout patients have high risk for cardiovascular events. Māori and Pacific populations have high risk for both gout and cardiovascular disease. The general aim of this study was to elucidate whether cardiovascular risk factors contribute to gout. New Zealand Caucasian and Māori/Pacific gout case and control sample sets were used. The serum lipid profile was investigated, including serum lipoprotein(a) (Lp(a)), measured with an enzyme-linked immunosorbant assay. Size exclusion chromatography was used on Māori and Pacific samples for detailed lipoprotein, apolipoprotein (apo) and lipid analyses. Increased prevalence for type III hyperlipoproteinemia (TIIIH; increased remnant lipoproteins which may result from the apo E isoform apo E2) and type IV hyperlipoproteinemia (TIVH; increased triglyceride (TG) due to increased very low density lipoprotein (VLDL) TG) was investigated. Single nucleotide polymorphisms (SNPs) in APOE determining isoforms APOE2 (rs7412) and APOE4 (rs429358) were genotyped. SNPs associated with an increased risk for cardiovascular disease were also genotyped, including rs3798220 and rs10455872 of LPA which also associate with Lp(a) levels, and rs1333049 of CDKN2BAS. Gout cases had increased total TG levels (p < 0.001) compared to gout controls in both Caucasian and Māori/Pacific sample sets. Māori and Pacific cases also had higher total and low density lipoprotein cholesterol, and lower high density lipoprotein cholesterol, than controls (p < 0.01). Chromatography analysis revealed a higher prevalence for TIVH in cases than controls (p < 0.001, odds ratio [95% confidence interval] = 7.7 [2.3 - 25.9]), due to an increased concentration of TG from an increased number of VLDL particles. No differences were found between VLDL cholesterol in cases and controls, indicating TIIIH prevalence was not increased in gout. Supporting this, APOE isoforms did not associate with gout. Lp(a) levels did not differ between Caucasian and Māori/Pacific subjects, nor by gout affliction. No associations were found between the two LPA SNPs and gout, or between the CDKN2BAS SNP and gout. The current study implicates that hypertriglyceridemia, inherent of the metabolic syndrome, is a linking factor between gout and cardiovascular disease. Future research exploring the relationship between the two diseases should be directed in this area, including testing genetic variants associated with hypertriglyceridemia for association with gout.