Zaragoza-García Oscar, Guzmán-Guzmán Iris Paola, Moreno-Godínez Ma Elena, Navarro-Zarza José Eduardo, Antonio-Vejar Verónica, Ramírez Mónica, Parra-Rojas Isela
Programa de Maestría en Ciencias Biomédicas, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero, México.
Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, CP. 39090, Chilpancingo, Guerrero, México.
Clin Rheumatol. 2021 Feb;40(2):741-752. doi: 10.1007/s10067-020-05218-w. Epub 2020 Jun 18.
INTRODUCTION/OBJECTIVE: Paraoxonase 1 (PON1) promotes antioxidant and antiatherogenic activity related to the hydrolysis of oxidized lipids of low-density lipoproteins. In rheumatoid arthritis (RA) patients, it has been reported that low PON1 activity is related to an impaired lipid profile, increasing cardiovascular risk (CVR). The goal of this study was to analyze the effect of common PON1 polymorphisms and haplotypes on enzymatic activity, PON1 serum levels (PON1s), and lipid parameters related to atherogenic profile in RA patients.
A cross-sectional study was carried out on 250 Mexican patients with RA. The lipid profile was determined by colorimetric tests. The PON1 activity (CMPAase) was measured by spectrophotometry. The levels of PON1s were determined by ELISA, and the polymorphisms in the PON-1 gene (-108C>T, L55M, and Q192R) were genotyped by the PCR-RFLP method. The haplotypes were estimated and statistical analysis was performed.
The median of the CMPAase activity and PON1 levels was 13.91 U/mL and 24.75 ng/mL, respectively. The CMPAase activity was significantly lower in carriers of -108TT and 192QQ genotypes (β = - 4.09, P = 0.001 and β = - 3.73, P = 0.002, respectively); moreover, the PON1 levels were lower in 192Q allele carriers (P < 0.01). The TLQ haplotype was associated with CMPAase activity < 13.91 U/mL (OR = 2.29, P < 0.001), as well as with levels of PON1s < 24.75 ng/mL (OR = 1.65, P = 0.017). In this study, the CMPAase activity (< 13.91 U/mL) showed a positive association with lower levels of high-density lipoprotein cholesterol (HDL-c; < 40/50 mg/dL), and with a triglycerides/HDL-c ratio > 3%, and a total cholesterol/HDL-c ratio > 4.5/5%, all representatives of an atherogenic risk lipid profile.
PON1 polymorphisms modulate the CMPAase activity and PON1 levels in Mexican patients with RA. The CMPAase activity < 13.91 U/mL is associated with an atherogenic lipid profile, independently of inflammation markers and treatment with anti-rheumatic drugs. Key Points •The haplotype TLQ is a marker for low PONase activity in rheumatoid arthritis. •The haplotype TLQ is a marker for low PON1 serum levels in rheumatoid arthritis. •The enzymatic PON1 activity represents the best marker for an atherogenic lipid profile in rheumatoid arthritis, in comparison with PON1 levels. •The haplotype TLQ is a marker of low PON1 activity, levels of PON1s, and atherogenic lipid profile, independent of treatment therapy in rheumatoid arthritis.
引言/目的：对氧磷酶1（PON1）通过水解低密度脂蛋白的氧化脂质来促进抗氧化和抗动脉粥样硬化活性。在类风湿关节炎（RA）患者中，已有报道称PON1活性降低与脂质状况受损有关，从而增加心血管风险（CVR）。本研究的目的是分析常见的PON1基因多态性和单倍型对RA患者酶活性、PON1血清水平（PON1s）以及与动脉粥样硬化相关的脂质参数的影响。
对250名墨西哥RA患者进行了一项横断面研究。通过比色法测定脂质状况。采用分光光度法测量PON1活性（CMPAase）。通过酶联免疫吸附测定（ELISA）确定PON1s水平，并采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法对PON-1基因的多态性（-108C>T、L55M和Q192R）进行基因分型。估计单倍型并进行统计分析。
CMPAase活性和PON1水平的中位数分别为13.91 U/mL和24.75 ng/mL。-108TT和192QQ基因型携带者的CMPAase活性显著较低（β分别为-4.09，P = 0.001和β为-3.73，P = 0.002）；此外，192Q等位基因携带者的PON1水平较低（P < 0.01）。TLQ单倍型与CMPAase活性<13.91 U/mL相关（比值比[OR]=2.29，P < 0.001），也与PON1s水平<24.75 ng/mL相关（OR = 1.65，P = 0.017）。在本研究中，CMPAase活性（<13.91 U/mL）与较低水平的高密度脂蛋白胆固醇（HDL-c；<40/50 mg/dL）、甘油三酯/HDL-c比值>3%以及总胆固醇/HDL-c比值>4.5/5%呈正相关，这些都是动脉粥样硬化风险脂质状况的代表指标。
PON1基因多态性可调节墨西哥RA患者的CMPAase活性和PON1水平。CMPAase活性<13.91 U/mL与动脉粥样硬化脂质状况相关，独立于炎症标志物和抗风湿药物治疗。要点：•TLQ单倍型是类风湿关节炎中PON酶活性低的标志物。•TLQ单倍型是类风湿关节炎中PON1血清水平低的标志物。•与PON1水平相比，酶促PON1活性是类风湿关节炎中动脉粥样硬化脂质状况的最佳标志物。•TLQ单倍型是类风湿关节炎中PON1活性、PON1s水平和动脉粥样硬化脂质状况低的标志物，独立于治疗方法。
