Apolipoprotein A5 gene polymorphism (rs662799) and cardiovascular disease in end-stage kidney disease patients

Plasma triglyceride (TG) levels are a significant risk factor for cardiovascular disease (CVD). The APOA5 gene is one of the crucial factors in plasma TG metabolism regulation. The rs662799 polymorphism in the APOA5 gene has been reported to be associated with cardiovascular disease. The goal of this study was to evaluate the potential association of this variant with CVD in patients with end-stage kidney disease.  METHODS: In this case-control study the polymorphism was analyzed using the PCR-RFLP method in 800 consecutive patients with ESKD and 500 healthy controls. The genotype and allele distribution was compared between subgroups of patients with CVD (552) versus those without CVD (248).

The frequency of the minor allele (C) in the healthy individuals was 9% compared to 12% in ESRD group (p = 0.09). The difference between groups was slightly higher for CC homozygote (3.5% versus 1.6%, p = 0.042). The ESKD patient group was analyzed according to the presence or absence of CVD. The significant differences in the polymorphism distribution were revealed in this analysis. The frequency of the C allele in the CVD + subgroup was 14% compared to 6% in CVD- patients (p = 0.001). In the CVD + subgroup the ORs (95% CI) for the C allele and CC genotype were 2.41 (1.61-3.6), p < 0.001 and 3.13 (1.07-9.14), p = 0.036, respectively. This indicates to the association of the variant C allele with cardiovascular disease in ESKD patients. The CC homozygotes have a threefold higher odds of CVD compared to TT homozygotes. The highest frequency of the C allele (18%) was observed in subgroup of patients with diabetic nephropathy, with OR (95% CI) 3.40 (2.13-5.43), p < 0.001.The presence of minor allele (CC and CT genotypes) was significantly associated with increased plasma triglyceride levels (p < 0.001 for both CVD + and CVD- groups).

The present study demonstrated the effect of rs662799 polymorphism on plasma TG levels and its association with the development of cardiovascular disease in ESKD patients.