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

doi:10.1177/1933719110374365

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 journal › Article › peer-review

4 Scopus citations

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 language	English (US)
Pages (from-to)	913-916
Number of pages	4
Journal	Reproductive Sciences
Volume	17
Issue number	10
DOIs	https://doi.org/10.1177/1933719110374365
State	Published - Oct 2010

Keywords

mitochondria
prematurity
progesterone

ASJC Scopus subject areas

Obstetrics and Gynecology

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10.1177/1933719110374365

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Manuck, T. A., Price, T. M., Thom, E., Meis, P. J., Dombrowski, M. P., Sibai, B., Spong, C. Y., Rouse, D. J., Iams, J. D., Simhan, H. N., O'Sullivan, M. J., Miodovnik, M., Leveno, K. J., Conway, D., Wapner, R. J., Carpenter, M., Mercer, B., Ramin, S. M., Thorp, J. M., & 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

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

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title = "Absence of mitochondrial progesterone receptor polymorphisms in women with spontaneous preterm birth",

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.",

keywords = "mitochondria, prematurity, progesterone",

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

year = "2010",

month = oct,

doi = "10.1177/1933719110374365",

language = "English (US)",

volume = "17",

pages = "913--916",

journal = "Reproductive Sciences",

issn = "1933-7191",

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T1 - Absence of mitochondrial progesterone receptor polymorphisms in women with spontaneous preterm birth

AU - Manuck, Tracy A.

AU - Price, Thomas M.

AU - Thom, Elizabeth

AU - Meis, Paul J.

AU - Dombrowski, Mitchell P.

AU - Sibai, Baha

AU - Spong, Catherine Y.

AU - Rouse, Dwight J.

AU - Iams, Jay D.

AU - Simhan, Hyagriv N.

AU - O'Sullivan, Mary J.

AU - Miodovnik, Menachem

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.

PY - 2010/10

Y1 - 2010/10

N2 - 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.

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.

KW - mitochondria

KW - prematurity

KW - progesterone

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

Abstract

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ASJC Scopus subject areas

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