Absence of mitochondrial progesterone receptor polymorphisms in women with spontaneous preterm birth

Tracy A. Manuck, Thomas M. Price, Elizabeth Thom, Paul J. Meis, Mitchell P. Dombrowski, Baha Sibai, Catherine Y. Spong, Dwight J. Rouse, Jay D. Iams, Hyagriv N. Simhan, Mary J. O'Sullivan, Menachem Miodovnik, Kenneth J. Leveno, Deborah Conway, Ronald J. Wapner, Marshall Carpenter, Brian Mercer, Susan M. Ramin, John M. Thorp, Alan M. Peaceman

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)913-916
Number of pages4
JournalReproductive Sciences
Volume17
Issue number10
DOIs
StatePublished - Oct 2010

Fingerprint

Premature Birth
Progesterone Receptors
Progesterone
Mitochondrial Genome
DNA
Saliva
Base Pairing
Multicenter Studies
Mitochondria
Placebos
Prospective Studies
Membranes

Keywords

  • mitochondria
  • prematurity
  • progesterone

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Manuck, T. A., Price, T. M., Thom, E., Meis, P. J., Dombrowski, M. P., Sibai, B., ... Peaceman, A. M. (2010). Absence of mitochondrial progesterone receptor polymorphisms in women with spontaneous preterm birth. Reproductive Sciences, 17(10), 913-916. https://doi.org/10.1177/1933719110374365

Absence of mitochondrial progesterone receptor polymorphisms in women with spontaneous preterm birth. / 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.

In: Reproductive Sciences, Vol. 17, No. 10, 10.2010, p. 913-916.

Research output: Contribution to journalArticle

Manuck, TA, Price, TM, Thom, E, Meis, PJ, Dombrowski, MP, Sibai, B, Spong, CY, Rouse, DJ, Iams, JD, Simhan, HN, O'Sullivan, MJ, Miodovnik, M, Leveno, KJ, Conway, D, Wapner, RJ, Carpenter, M, Mercer, B, Ramin, SM, Thorp, JM & Peaceman, AM 2010, 'Absence of mitochondrial progesterone receptor polymorphisms in women with spontaneous preterm birth', Reproductive Sciences, vol. 17, no. 10, pp. 913-916. https://doi.org/10.1177/1933719110374365
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. / Absence of mitochondrial progesterone receptor polymorphisms in women with spontaneous preterm birth. In: Reproductive Sciences. 2010 ; Vol. 17, No. 10. pp. 913-916.
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abstract = "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.",
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AU - Price, Thomas M.

AU - Thom, Elizabeth

AU - Meis, Paul J.

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AU - Sibai, Baha

AU - Spong, Catherine Y.

AU - Rouse, Dwight J.

AU - Iams, Jay D.

AU - Simhan, Hyagriv N.

AU - O'Sullivan, Mary J.

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AU - Leveno, Kenneth J.

AU - Conway, Deborah

AU - Wapner, Ronald J.

AU - Carpenter, Marshall

AU - Mercer, Brian

AU - Ramin, Susan M.

AU - Thorp, John M.

AU - Peaceman, Alan M.

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AB - 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.

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