Absence of mitochondrial progesterone receptor polymorphisms in women with spontaneous preterm birth.
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.
Manuck
Tracy A
TA
Eunice Kennedy Shriver NICHD MFMU Network, Bethesda, MD, USA. tracy.manuck@hsc.utah.edu
Price
Thomas M
TM
Thom
Elizabeth
E
Meis
Paul J
PJ
Dombrowski
Mitchell P
MP
Sibai
Baha
B
Spong
Catherine Y
CY
Rouse
Dwight J
DJ
Iams
Jay D
JD
Simhan
Hyagriv N
HN
O'Sullivan
Mary J
MJ
Miodovnik
Menachem
M
Leveno
Kenneth J
KJ
Conway
Deborah
D
Wapner
Ronald J
RJ
Carpenter
Marshall
M
Mercer
Brian
B
Ramin
Susan M
SM
Thorp
John M
JM
Peaceman
Alan M
AM
D000595:Amino Acid Sequence; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics*; D011446:Prospective Studies; D011980:Receptors, Progesterone / Q000235:genetics*; D017422:Sequence Analysis, DNA
D004272:DNA, Mitochondrial; D011980:Receptors, Progesterone