Absence of Mitochondrial Progesterone Receptor Polymorphisms in Women With Spontaneous Preterm Birth

• Published in: Reproductive sciences (Thousand Oaks, Calif.) Calif.), 2010-10, Vol.17 (10), p.913-916
• Main Authors: Manuck, Tracy A., Price, Thomas M., Thom, Elizabeth, Meis, Paul J., Dombrowski, Mitchell P., Sibai, Baha, Spong, Catherine Y., Rouse, Dwight J., Iams, Jay D., Simhan, Hyagriv N., O'Sullivan, Mary J., Miodovnik, Menachem, Leveno, Kenneth J., Conway, Deborah, Wapner, Ronald J., Carpenter, Marshall, Mercer, Brian, Ramin, Susan M., Thorp, John M., Peaceman, Alan M.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Biological and medical sciences; Diseases of mother, fetus and pregnancy; DNA, Mitochondrial - chemistry; DNA, Mitochondrial - genetics; Embryology; Female; Genetic Variation - genetics; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Medicine & Public Health; Molecular Sequence Data; Obstetrics/Perinatology/Midwifery; Polymerase Chain Reaction; Polymorphism, Genetic - genetics; Pregnancy; Pregnancy. Fetus. Placenta; Premature Birth - genetics; Prospective Studies; Receptors, Progesterone - genetics; Reproductive Medicine; Sequence Analysis, DNA
• ISSN: 1933-7191; 1933-7205; 1933-7205
• DOI: 10.1177/1933719110374365

Objective: The truncated mitochondrial progesterone receptor (PR-M) is homologous to nuclear PRs with the exception of an amino terminus hydrophobic membrane localization sequence, which localizes PR-M to mitochondria. Given the matrilineal inheritance of both spontaneous preterm birth (SPTB) and the mitochondrial genome, we hypothesized that (a) PR-M is polymorphic and (b) PR-M localization sequence polymorphisms could result in variable progesterone-mitochondrial effects and variable responsiveness to progesterone prophylaxis. Methods: Secondary analysis of DNA from women enrolled in a multicenter, prospective, study of 17 alpha-hydroxyprogesterone caproate (17OHPC) versus placebo for the prevention of recurrent SPTB. DNA was extracted from stored saliva. Results: The PR-M localization sequence was sequenced on 344 patients. Sequences were compared with the previously published 48 base-pair sequence, and all were identical. Conclusions: We did not detect genetic variation in the mitochondrial localization sequence of the truncated PR-M in a group of women at high risk for SPTB.