Guardiola Montse, Ferré Raimon, Salazar Juliana, Alonso-Villaverde Carlos, Coll Blai, Parra Sandra, Masana Lluís, Ribalta Josep
Institut de Recerca en Ciències de la Salut, Hospital Universitari de Sant Joan de Reus, Universitat Rovira i Virgili, Reus, Spain.
Clin Chem. 2006 Oct;52(10):1914-9. doi: 10.1373/clinchem.2006.069583. Epub 2006 Aug 3.
Hyperlipidemia associated with the protease inhibitor (PI) component of highly active antiretrovial treatment can lead to accelerated atherosclerosis. The apolipoprotein A-V (APOA5) gene, which affects VLDL production and lipolysis, may play a role in PI-induced hyperlipidemia, particularly in individuals with the APOA5-1131T-->C genotype.
We measured lipoprotein changes in HIV-positive patients (n = 229) who had been followed for 5 years. For statistical analyses, we segregated the patients with respect to PI treatment and APOA5-1131T-->C genotype.
The frequency of the C allele was 0.08, similar to that in the general population. We found a strong effect of the APOA5-1131T-->C genotype among patients receiving PIs. Carriers of the C allele had consistently increased mean (SD) triglyceride concentrations compared with noncarriers after 1 year [2.11 (1.62) vs 3.71 (4.27) mmol/L; P = 0.009], 2 years [2.48 (2.09) vs 4.02 (4.05) mmol/L, P = 0.050], 3 years [2.32 (1.71) vs 4.13 (4.26) mmol/L; P = 0.013], 4 years [2.90 (2.95) vs 5.35 (7.12) mmol/L; P was not significant], and 5 years [4.25 (5.58) vs 9.23 (9.63) mmol/L; P was not significant]. We observed the same effect on total cholesterol concentrations: after 1 year [4.93 (1.31) vs 5.87 (1.66) mmol/L; P = 0.006], 2 years [5.03 (1.12) vs 6.42 (2.48) mmol/L; P = 0.001], 3 years [5.11 (1.17) vs 6.38 (2.43) mmol/L; P = 0.009], 4 years [5.49 (1.71) vs 6.78 (3.03) mmol/L; P was not significant], and 5 years [5.56 (1.75) vs 7.90 (3.60) mmol/L; P was not significant]. HDL cholesterol showed a progressive reduction, leading to a considerably higher cholesterol/HDL cholesterol ratio after 3 years.
Variability in the APOA5 gene predisposes patients with HIV, particularly those treated with PI, to severe hyperlipidemia.
高效抗逆转录病毒治疗中与蛋白酶抑制剂（PI）成分相关的高脂血症可导致动脉粥样硬化加速。载脂蛋白A-V（APOA5）基因影响极低密度脂蛋白（VLDL）的产生和脂解，可能在PI诱导的高脂血症中起作用，尤其是在具有APOA5-1131T→C基因型的个体中。
我们对229名接受了5年随访的HIV阳性患者的脂蛋白变化进行了测量。为进行统计分析，我们根据PI治疗和APOA5-1131T→C基因型对患者进行了分类。
C等位基因的频率为0.08，与一般人群相似。我们发现APOA5-1131T→C基因型在接受PI治疗的患者中具有显著影响。1年后，C等位基因携带者的平均（标准差）甘油三酯浓度持续高于非携带者[2.11（1.62）对3.71（4.27）mmol/L；P = 0.009]，2年后[2.48（2.09）对4.02（4.05）mmol/L，P = 0.050]，3年后[2.32（1.71）对4.13（4.26）mmol/L；P = 0.013]；4年后[2.90（2.95）对5.35（7.12）mmol/L；P无统计学意义]，5年后[4.25（5.58）对9.23（9.63）mmol/L；P无统计学意义]。我们观察到对总胆固醇浓度有相同的影响：1年后[4.93（1.31）对5.87（1.66）mmol/L；P = 0.006]，2年后[5.03（1.12）对6.42（2.48）mmol/L；P = 0.001]，3年后[5.11（1.17）对6.38（2.43）mmol/L；P = 0.009]，4年后[5.49（1.71）对6.78（3.03）mmol/L；P无统计学意义]，5年后[5.56（1.75）对7.90（3.60）mmol/L；P无统计学意义]。高密度脂蛋白胆固醇呈逐渐降低趋势，导致3年后胆固醇/高密度脂蛋白胆固醇比值显著升高。
APOA5基因的变异性使HIV患者，尤其是接受PI治疗的患者易患严重高脂血症。
