The association of single-nucleotide polymorphisms in the oxytocin receptor and G protein-coupled receptor kinase 6 (GRK6) genes with oxytocin dosing requirements and labor outcomes.
The association of single-nucleotide polymorphisms in the oxytocin receptor and G protein-coupled receptor kinase 6 (GRK6) genes with oxytocin dosing requirements and labor outcomes.
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DOI：
10.1016/j.ajog.2017.05.023
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发表时间：
2017-09
影响因子：
9.8
通讯作者：
Swamy GK
中科院分区：
文献类型：
--
作者：
Grotegut CA;Ngan E;Garrett ME;Miranda ML;Ashley-Koch AE;Swamy GK
催产素是一种有效的子宫扩张剂，广泛用于诱导和增加分娩。催产素的治疗指数很窄，每个女性的最佳剂量差别很大。本研究的目的是确定催产素受体（OXTR）或调节OXTR脱敏的G蛋白偶联受体激酶6 （GRK6）基因的遗传变异是否可以解释催产素剂量和近期引产妇女分娩结果的差异。居住在北卡罗来纳州达勒姆县的单胎妊娠孕妇被前瞻性地纳入健康妊娠，健康婴儿队列研究的一部分。在36周或更大时间引产的妇女使用TaqMan方法对OXTR中的18个单倍型标记（ht）单核苷酸多态性（SNPs）和GRK6中的7个htsnp进行基因分型。采用线性回归分析母体基因型与最大催产素输注率、总催产素剂量和产程的关系。采用Logistic回归检验母体基因型与分娩方式的相关性。对于每个结果，采用逆向选择技术来控制重要的混杂变量，并采用加性遗传模型。由于人群中等位基因频率的差异，所有模型都包含了种族/民族，并使用了多重测试的Bonferroni校正。从482名在36周或以上进行引产的妇女中获得了DNA。检测了OXTR中的18个snp和GRK6中的7个snp。OXTR中的5个snp与催产素最大输注率有显著性差异，OXTR中的2个snp与催产素总剂量相关。OXTR的1个SNP和GRK6的2个SNP与产程相关，其中1个符合多重检测阈值（p=0.0014, rs2731664 [GRK6]， AA、AC和CC基因型的平均产程分别为17.7小时、20.2小时和23.5小时）。三个snp，两个在OXTR中，一个在GRK6中，显示出与传递方式的名义意义。在近期引产的妇女中，OXTR和GRK6的遗传变异与催产素所需的量、分娩持续时间和剖宫产的风险有关。随着进一步的研究，药物基因组学方法可能被用于开发个性化治疗，以提高引产妇女的安全性和有效性。
Oxytocin is a potent uterotonic agent that is widely used for induction and augmentation of labor. Oxytocin has a narrow therapeutic index and the optimal dosing for any individual woman varies widely. The objective of this study was to determine if genetic variation in the oxytocin receptor (OXTR) or in the gene encoding G protein-coupled receptor kinase 6 (GRK6), which regulates desensitization of the OXTR, could explain variation in oxytocin dosing and labor outcomes among women being induced near term. Pregnant women with a singleton gestation residing in Durham County, NC were prospectively enrolled as part of the Healthy Pregnancy, Healthy Baby cohort study. Those women undergoing an induction of labor at 36 weeks or greater were genotyped for 18 haplotype tagging (ht) single nucleotide polymorphisms (SNPs) in OXTR and 7 htSNPs in GRK6 using TaqMan assays. Linear regression was used to examine the relationship between maternal genotype and maximal oxytocin infusion rate, total oxytocin dose received, and duration of labor. Logistic regression was used to test for association of maternal genotype with mode of delivery. For each outcome, backward selection techniques were utilized to control for important confounding variables and additive genetic models were employed. Race/ethnicity was included in all models due to differences in allele frequencies across populations and Bonferroni correction for multiple testing was used. DNA was available from 482 women undergoing induction of labor at 36 weeks or greater. 18 SNPs within OXTR and 7 SNPs within GRK6 were examined. Five SNPs in OXTR showed nominal significance with maximal infusion rate of oxytocin and two SNPs in OXTR were associated with total oxytocin dose received. One SNP in OXTR and two SNPs in GRK6 were associated with duration of labor, one of which met the multiple testing threshold (p=0.0014, rs2731664 [GRK6], mean duration of labor 17.7 hours vs. 20.2 hours vs. 23.5 hours for AA, AC and CC genotypes, respectively). Three SNPs, two in OXTR and one in GRK6, showed nominal significance with mode of delivery. Genetic variation in OXTR and GRK6 is associated with the amount of oxytocin required, as well as the duration of labor and risk for cesarean delivery among women undergoing induction of labor near term. With further research, pharmacogenomic approaches may potentially be utilized to develop personalized treatment to improve safety and efficacy outcomes among women undergoing induction of labor.
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DOI：
10.1016/s0002-9378(84)90355-7
发表时间：
1984-01-01
影响因子：
9.8
作者：
SEITCHIK, J;AMICO, J;CASTILLO, M
通讯作者：
CASTILLO, M
影响因子：
2
作者：
Swamy, Geeta K.;Garrett, Melanie E.;Miranda, Marie Lynn;Ashley-Koch, Allison E.
通讯作者：
Ashley-Koch, Allison E.
DOI：
10.3390/ijerph8030698
发表时间：
2011-03
影响因子：
--
作者：
Miranda ML;Edwards S;Maxson PJ
通讯作者：
Maxson PJ
影响因子：
--
作者：
Grotegut, Chad A.;Mao, Lan;Murtha, Amy P.
通讯作者：
Murtha, Amy P.
影响因子：
4.8
作者：
Oakley, RH;Laporte, SA;Caron, MG
通讯作者：
Caron, MG