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Catechol-O-methyltransferase (COMT) Genotype is Highly Predictive of Prolonged Induction and Augmentation of Labor
Abstract Number: T-22
Abstract Type: Original Research
Background: Failed induction of labor is a common cause of cesarean section. Circulating epinephrine at physiological concentrations can inhibit uterine contractility via a beta-2 adrenoceptor mechanism. The enzyme COMT metabolizes systemic epinephrine. We hypothesized that polymorphisms (SNPS) in the COMT gene known to affect enzyme activity would modify the uterine contractile response to exogenous oxytocin used for induction and augmentation via alterations in uterine contractility related to systemic epinephrine.
Methods: We performed a secondary analysis of a cohort of 704 nulliparous women who underwent vaginal delivery at a major New York hospital. Oxytocin was administered according to institutional protocol with escalating doses to achieve adequate uterine contraction. We evaluated the effect of 3 common SNPs in the COMT gene that are known to alter protein function on the duration of oxytocin administration with Wilcoxon’s Rank Sum Test using R-programing language.
Results: We found a correlation between expression of COMT rs6269 G allele and the amount of time a patient spent on an escalating infusion of oxytocin for induction and or augmentation (Figure 1 rs6269, P= 0.035). Genotype at COMT rs4646312 and rs4633 were not associated with oxytocin requirement.
Discussion: There are many SNPs that are in strong linkage disequilibrium within the COMT gene1. Further analysis of haplotypes important for COMT gene activity are warranted to determine whether any associated with reduced enzyme activity are present. Reduced COMT enzyme activity would be expected to cause increased concentrations of circulating catecholamines that would induce tonic relaxation, perhaps resulting in the need for increased oxytocin, or increased risk of induction failure. These findings should be confirmed in independent candidate gene or exome- or genome-wide studies.
1. Belfer I, et al.Pain modality- and sex specific effects of COMT genetic functional variants. Pain 2013;154:1368–76.