PPARα-L162V 多态性与利培酮治疗后血浆低密度脂蛋白胆固醇水平升高之间的关系

IF 3
Sergej Nadalin , Lena Zatković , Vjekoslav Peitl , Dalibor Karlović , Maja Vilibić , Ante Silić , Sanja Dević Pavlić , Alena Buretić-Tomljanović
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引用次数: 0

摘要

过氧化物酶体增殖激活受体α(PPARα)和抗精神病药物都会影响多不饱和脂肪酸(PUFA)的平衡,因此 PPARα 的多态性可能与抗精神病药物的治疗反应有关。在此,我们研究了PPARα的功能性亮氨酸162缬氨酸(L162V)多态性是否会影响一组精神病患者(N = 186)的抗精神病治疗,以及接受利培酮、帕利培酮或联合治疗的患者亚组(N = 65)的抗精神病治疗。通过聚合酶链式反应分析,对未服用抗精神病药的首发患者和未坚持治疗的慢性患者进行了基因分型。在基线和接受各种抗精神病药物治疗 8 周后,我们评估了患者的阳性和阴性综合征量表 (PANSS) 评分、PANSS 因素和代谢综合征相关参数,包括空腹血浆脂质和葡萄糖水平以及体重指数。在所有患者组中,PPARα多态性对PANSS精神病理学和代谢参数没有影响。然而,在接受利培酮、帕利培酮或联合治疗的亚组患者中,PPARα多态性影响了血浆低密度脂蛋白胆固醇的变化。具体而言,与PPARα-L162L同源患者相比,PPARα-L162V杂合患者在接受抗精神病药物治疗后,其低密度脂蛋白胆固醇水平的升高幅度明显更高。PPARα 多态性具有很强的效应大小,但对低密度脂蛋白胆固醇水平变化的贡献相对较弱(∼12.8%)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
An association between PPARα-L162V polymorphism and increased plasma LDL cholesterol levels after risperidone treatment

Peroxisome proliferator-activated receptor alpha (PPARα) and antipsychotic medications both influence polyunsaturated fatty acids (PUFA) homeostasis, and thus PPARα polymorphism may be linked to antipsychotic treatment response. Here we investigated whether the functional leucine 162 valine (L162V) polymorphism in PPARα influenced antipsychotic treatment in a group of psychosis patients (N = 186), as well as in a patient subgroup with risperidone, paliperidone, or combination treatment (N = 65). Antipsychotic-naïve first-episode patients and nonadherent chronic individuals were genotyped by polymerase chain reaction analysis. At baseline, and after 8 weeks of treatment with various antipsychotic medications, we assessed the patients’ Positive and Negative Syndrome Scale (PANSS) scores; PANSS factors; and metabolic syndrome-related parameters, including fasting plasma lipid and glucose levels, and body mass index. In the total patient group, PPARα polymorphism did not affect PANSS psychopathology or metabolic parameters. However, in the subgroup of patients with risperidone, paliperidone, or combination treatment, PPARα polymorphism influenced changes in plasma LDL cholesterol. Specifically, compared to PPARα-L162L homozygous patients, PPARα-L162V heterozygous individuals exhibited significantly higher increases of LDL cholesterol levels after antipsychotic treatment. The PPARα polymorphism had a strong effect size, but a relatively weak contribution to LDL cholesterol level variations (∼12.8 %).

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来源期刊
Prostaglandins, leukotrienes, and essential fatty acids
Prostaglandins, leukotrienes, and essential fatty acids Clinical Biochemistry, Endocrinology, Diabetes and Metabolism
CiteScore
5.30
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0.00%
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审稿时长
64 days
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