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38: The relationship between polymorphisms in the human progesterone receptor and clinical response to 17 alpha-hydroxyprogesterone caproate for the prevention of recurrent spontaneous preterm birth

      Objective

      17 alpha-hydroxyprogesterone caproate (17OHPC) has been shown to reduce the recurrence risk of spontaneous preterm birth (SPTB). Our aim was to assess if women with single nucleotide polymorphisms (SNPs) in the human progesterone receptor (hPR) are more or less likely to respond to 17OHPC for the prevention of recurrent SPTB.

      Study Design

      Secondary analysis of 463 women enrolled in a multicenter, prospective, double-blind study of 17OHPC vs. placebo for the prevention of recurrent SPTB. Individuals were genotyped with 20 SNPs in the hPR gene. Allele and genotype frequencies were calculated and evaluated for evidence of genetic predisposition to 17OHPC response.

      Results

      DNA was extracted and genotyped from the saliva of 335 patients; 231 (69%) received 17OHPC (cases), and 104 (31%) received placebo (controls). All SNPs were in Hardy-Weinberg equilibrium. SPTB rates in each group were similar to the original cohort. Clinical characteristics, racial distribution, and allele frequencies were not significantly different between cases and controls. The majority (60.3%) of patients in our cohort were African-American.
      SPTB was less common among women who received 17OHPC compared to controls regardless of allele status for all SNPs. However, among African-American women who received 17OHPC, those who were carriers of the minor allele (G) in SNP rs471767 (A/G) were more likely to have SPTB compared to those carrying the major allele (38% preterm <37 weeks gestation vs. 22% respectively, p=0.007, odds ratio 2.2, 95% CI: 1.2-3.9). SPTB <32 weeks gestation was also more likely in non-African-American women who received 17OHPC for SNPs rs503362 (G allele), rs471767 (A allele), and rs578029 (T allele); p=0.009, 0.029, & 0.048 respectively.

      Conclusion

      The clinical efficacy of 17OHPC for prevention of recurrent SPTB may be altered by polymorphisms in the hPR gene. Further analysis of interactions between the hPR SNPs (haplotypes) is ongoing and could reveal a more specific 17OHPC response profile.