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Science/Tech See other Science/Tech Articles Title: Genes May Play a Role in Response to Preemie Prevention Treatment SMFM: Society for Maternal-Fetal Medicine Meeting SMFM: Genes May Play a Role in Response to Preemie Prevention Treatment By Todd Neale, Staff Writer, MedPage Today SAN DIEGO, Feb. 3 -- Genetic variation in the human progesterone receptor may explain why treatment to prevent recurrent preterm birth does not work in some women, researchers found. Certain single nucleotide polymorphisms seemed to play a role in the efficacy of 17 alpha-hydroxyprogesterone caproate, said Tracy Manuck, M.D., of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network in Bethesda, Md. She described the results as exploratory, but told attendees at the Society for Maternal-Fetal Medicine meeting that "further studies may lead to the creation of a response panel, enabling clinicians to direct therapy to those women most likely to benefit." "This research provides important preliminary information and direction for future investigation of progesterone receptor gene variation and the etiology and treatment of preterm birth," she said. Dr. Manuck and colleagues conducted a secondary analysis of women who were enrolled in a prospective, multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy of 17 alpha-hydroxyprogesterone caproate for preventing a second preterm birth in women who had previously had one. That study found that the drug reduced the rate of recurrent preterm birth by about 33%, but Dr. Manuck and her colleagues wanted to find out whether genetic variation in the targeted receptor modulated its benefits. So they extracted DNA from stored saliva samples for 258 women who had received active treatment and 131 who had received placebo. Most of the women (59.6%) were black, 39.6% gave birth before 37 weeks gestation, and 12.1% gave birth before 32 weeks gestation. More than a quarter (28%) had had more than one previous spontaneous preterm birth. The researchers examined 20 SNPs on the progesterone receptor, a handful of which were significantly correlated with response to treatment. Among black women who were homozygous for the major allele on SNP rs471767, those who received active treatment had a significantly reduced rate of preterm birth compared with those who received placebo (21% versus 60%, P=0.0229). Those who had at least one copy of the minor allele, however, did not derive any benefit from active treatment. Looking at another SNP -- rs578029 -- the researchers found that among black women who had a least one copy of the major allele, those who received active treatment had a significant reduction in preterm birth (25% versus 55%, P=0.0289). Those who had two copies of the minor allele did not benefit from treatment. Similar relationships were found among non-black women who gave birth at less than 32 weeks gestation. Those who had a least one copy of the minor allele on yet another SNP -- rs503362 -- had a significant reduction with active treatment (2.6% versus 17.4%, P=0.0263). Similarly, non-black women who had at least one copy of the minor allele on a fourth SNP -- rs666553 -- had a significant reduction in very preterm birth compared with placebo (3.4% versus 26.7%, P=0.0382). Among non-black women who were homozygous for the major allele on both of those SNPs, rates of very preterm birth were similar in those who received active treatment and those who received placebo. Dr. Manuck said the findings indicated that "the clinical efficacy of 17 alpha-hydroxyprogesterone caproate for prevention of recurrent preterm birth may be altered by polymorphisms in the progesterone receptor gene."
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