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.

Figure 1

Gel electrophoresis (1.5% agarose gel) of the PR-M localization sequence demonstrating isolation of the 48 base-pair PCR amplification product used for sequencing. The arrow indicates the gel position of 50 base pairs (15 ng). Thirteen samples are shown, with 1 sample per lane. PR-M indicates mitochondrial progesterone receptor; PCR, polymerase chain reaction.

Figure 2

The 16 novel amino acids (and 48 corresponding base pairs) comprising the hydrophobic localization sequence of progesterone-receptor M (PR-M). This sequence was identical in all 351 genotyped patients.