Oxytocin and catechol-O-methyltransferase receptor genotype predict the length of the first stage of labor

Terkawi, Abdullah Sulieman; Jackson, William M.; Thiet, Mari-Paule; Hansoti, Shehnaz; Tabassum, Rabeena; Flood, Pamela

doi:10.1016/j.ajog.2012.06.079

Cited by 25 publications

(24 citation statements)

References 33 publications

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“…17 rs53576 is a widely studied common variant in the third intron of OXTR and genetic variation at this SNP has been associated with differences in social behavior. 18 The haplotype tagging SNPs chosen in our study were all in the 3’-UTR or intronic regions of the genes, thus it is not known if they directly affect protein structure or function.…”

Section: Commentmentioning

confidence: 99%

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

Grotegut

Ngan

Garrett

et al. 2017

American Journal of Obstetrics and Gynecology

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Background 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. Objective 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. Study Design 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. Results 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. Conclusions 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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Section: Commentmentioning

confidence: 99%

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

Grotegut

Ngan

Garrett

et al. 2017

American Journal of Obstetrics and Gynecology

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“…8 Are receptor genotypes for oxytocin and catecholamine-metabolising enzymes altered as we get older? 9 What is the role of paternal age on outcome? How does the exposure to environmental toxins and radiation affect pregnancy in older women?…”

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confidence: 99%

Does maternal age affect pregnancy outcome?

Cohen

2014

BJOG

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Please cite this paper as: Cohen WR. Does maternal age affect pregnancy outcome ?. BJOG 2014;121:252-254. The question, 'Does maternal age affect pregnancy outcome?' is a simple one. Its answer is, however, deceptively complex, and has defied complete understanding despite several generations of research. It remains, nevertheless, a question of consequence because it addresses issues of considerable biological and clinical importance.It has long been recognised that advanced maternal age (variously defined, but generally including women over age 35 years at delivery) is associated with an elevated risk of sundry adverse pregnancy outcomes when compared with younger (post-adolescent) women. 1,2The sway of maternal age has assumed increasing importance in recent decades. In most of the industrialised world the confluence of several social and demographic trends has resulted in an increasing number of women becoming pregnant late in their reproductive lives. The rise of feminism facilitated better educational opportunities and broader career choices for women, who now tend to marry later in life than did their forebears. These societal trends, combined with the availability of effective birth control and sophisticated treatments for infertility, have resulted in an expanding population of women who first attempt pregnancy after age 35. Primigravidity after 40 is no longer uncommon and, usually with the help of assisted reproductive technology, we not infrequently see women pregnant in their sixth decade. While many pregnancies in older women are the result of personal choice, others are not voluntary. Infertility or illness can delay conception.Pregnancy at the opposite pole of the reproductive age spectrum is also of concern, and many studies suggest that being an early adolescent is a noteworthy risk factor for unfavourable pregnancy outcome. To what degree the risks of teenage pregnancy are related to insufficient maturation of the reproductive system is unclear.Concerns about the potential adverse consequences of pregnancy near the borders of a woman's reproductive life are addressed in two articles in this issue of BJOG. These confirm our existing understanding about advanced and early reproductive age pregnancy. Vaughan et al.3 examined the association between maternal age extremes and pregnancy outcome among 36 916 nulliparas in an Irish tertiary-care hospital. They found that, when compared with an optimal age group of 20-34 years, being <17 years of age increased the odds for preterm birth by about 80%. Newborns of mothers >40 were about 35% more likely to require intensive care, and 70% more likely to have an anomaly. The caesarean delivery rate increased in direct proportion to age, and was 54.4% in the over-40 group, nearly five-fold higher than in the adolescent group. Only about a quarter of the over-40 group escaped caesarean or operative vaginal delivery, a perplexing and disquieting finding.A Finnish population study by Klemetti et al. 4 addressed the issue by comparing obstetric care and outcom...

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“…They found that women who were homozygous for 'G' at OXTR gene rs53576 transitioned to active labor later and thus had slower labor. Although there is no literature to date on the genetic variation in response to oxytocin, this information as well as other studies of OXTR gene polymorphisms may lead to advancements in the prescription of this commonly used adjunct in labor management [41].…”

Section: Oxytocinmentioning

confidence: 98%

Pharmacotherapy options for labor induction

Sheibani¹

2015

Expert Opinion on Pharmacotherapy

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Prostaglandins and oxytocin have been proven to be safe and effective methods of induction. However, the optimal medication for induction is yet to be determined. Although there are currently no pharmacogenomic findings that affect dosing of either prostaglandins or oxytocin, this is a growing area of research. In the near future, it may become clear that there is no 'one regimen for all' when selecting an induction or cervical ripening agent, or any other pharmaceutical altogether.

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Oxytocin and catechol-O-methyltransferase receptor genotype predict the length of the first stage of labor

Cited by 25 publications

References 33 publications

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

Does maternal age affect pregnancy outcome?

Pharmacotherapy options for labor induction

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