协会在细胞色素P450 3 a中,孕激素受体多态性,等离子体17-alpha己酸羟孕酮酯的浓度,并自发早产。

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布斯托斯ML, Caritis SN、雅布伦斯基KA Reddy嗯,Sorokin Y, Manuck T,走MW,超越国界RJ,艾玛JD,木匠兆瓦,Peaceman,美世BM, Sciscione,唤醒DJ,白木SM

协会在细胞色素P450 3 a中,孕激素受体多态性,等离子体17-alpha己酸羟孕酮酯的浓度,并自发早产。

比较。Gynecol。2017年9月,217 (3):369. e1 - 369. e9。doi: 10.1016 / j.ajog.2017.05.019。Epub 2017年5月15日。

PubMed ID

28522317 (在PubMed

]

文摘

背景:婴儿出生< 37周的妊娠并发症以来公共卫生关注的早产的主要原因是在5岁以下儿童死亡率和发病率和终身残疾的主要原因。管理17-alpha己酸羟孕酮酯降低早产33%女性自发早产的历史。我们之前证明等离子体浓度17-alpha己酸羟孕酮酯相差很大在孕妇和女性与17-alpha己酸羟孕酮酯等离子体浓度最低的四分之一的自发早产率40% vs 25%的利率在那些女性更高的浓度。因此,等离子体浓度决定药物疗效的一个重要因素,但原因17-alpha己酸羟孕酮酯等离子体浓度变化还不清楚。主要是,17-alpha己酸羟孕酮酯是由CYP3A4和CYP3A5酶代谢的。目的:我们试图:(1)确定之间的关系17-alpha己酸羟孕酮酯血浆浓度和单核苷酸多态性在CYP3A4和CYP3A5;(2)测试孕激素受体单核苷酸多态性之间的关系和自发早产;和(3)测试的血浆浓度之间的联系是否17-alpha己酸羟孕酮酯和自发早产不同孕酮受体单核苷酸多态性。研究设计:二次分析,我们在268年评估遗传多态性孕妇接受17-alpha己酸羟孕酮酯,参与一个安慰剂对照试验来评估补充ω- 3的好处与自发早产史的女性。槽等离子体浓度17-alpha己酸羟孕酮酯之间测量25 - 28周的妊娠后至少5注射17-alpha己酸羟孕酮酯。 We extracted DNA from maternal blood samples and genotyped the samples using TaqMan (Applied Biosystems, Foster City, CA) single nucleotide polymorphism genotyping assays for the following single nucleotide polymorphisms: CYP3A4*1B, CYP3A4*1G, CYP3A4*22, and CYP3A5*3; and rs578029, rs471767, rs666553, rs503362, and rs500760 for progesteronereceptor. We adjusted for prepregnancy body mass index, race, and treatment group in a multivariable analysis. Differences in the plasma concentrations of 17-alpha hydroxyprogesterone caproate by genotype were evaluated for each CYP single nucleotide polymorphism using general linear models. The association between progesterone receptor single nucleotide polymorphisms and frequency of spontaneous preterm birth was tested using logistic regression. A logistic model also tested interaction between 17-alpha hydroxyprogesterone caproate concentrations with each progesterone receptor single nucleotide polymorphism for the outcome of spontaneous preterm birth. RESULTS: The association between CYP single nucleotide polymorphisms *22, *1G, *1B, and *3 and trough plasma concentrations of 17-alpha hydroxyprogesterone caproate was not statistically significant (P = .68, .44, .08, and .44, respectively). In an adjusted logistic regression model, progesterone receptor single nucleotide polymorphisms rs578029, rs471767, rs666553, rs503362, and rs500760 were not associated with the frequency of spontaneous preterm birth (P = .29, .10, .76, .09, and .43, respectively). Low trough plasma concentrations of 17-alpha hydroxyprogesterone caproate were statistically associated with a higher frequency of spontaneous preterm birth (odds ratio, 0.78; 95% confidence ratio, 0.61-0.99; P = .04 for trend across quartiles), however no significant interaction with the progesterone receptor single nucleotide polymorphisms rs578029, rs471767, rs666553, rs503362, and rs500760 was observed (P = .13, .08, .10, .08, and .13, respectively). CONCLUSION: The frequency of recurrent spontaneous preterm birth appears to be associated with trough 17-alpha hydroxyprogesterone caproate plasma concentrations. However, the wide variation in trough 17-alpha hydroxyprogesterone caproate plasma concentrations is not attributable to polymorphisms in CYP3A4 and CYP3A5 genes. Progesterone receptor polymorphisms do not predict efficacy of 17-alpha hydroxyprogesterone caproate. The limitations of this secondary analysis include that we had a relative small sample size (n = 268) and race was self-reported by the patients.

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药物酶

药物	酶	类	生物	药理作用	行动
羟孕酮	细胞色素P450 3 a4	蛋白质	人类	没有	底物	细节
孕酮	细胞色素P450 3 a5	蛋白质	人类	未知的	底物	细节