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49: A polymorphism in a gene coding for the NALP3-inflammasome is associated with preterm premature rupture of the membranes

      Objective

      A cytoplasmic structure called the inflammasome has recently been demonstrated to regulate the production and release of interleukin-1beta (IL-1beta). A key structural component of the inflammasome is a protein called NALP3, a product of the CIAS1 gene. A polymorphism in the CIAS1 gene results in altered gene expression and variations in IL-1beta production. We hypothesized that, since IL-1beta is a prime trigger of preterm labor, a womans CIAS1 genotype may influence susceptibility to an adverse pregnancy outcome.

      Study design

      Buccal swabs were collected from women with preterm (n= 92) and term delivery (n=121). DNA was extracted and tested by polymerase chain reaction for a length polymorphism in intron 4 of the CIAS1 gene. Clinical outcomes were obtained only after completion of all testing.

      Results

      Homozygosity for the 12 unit repeat was strongly associated with a term birth (P<.0001). Conversely, homozygosity or heterozygosity for the 6, 7 or 9 unit repeats was associated with preterm birth (P=.01). Differentiating the preterm birth patients into those with preterm premature rupture of membranes (pPROM, n=21), spontaneous preterm birth (n=21) or indicated preterm birth (n=83) revealed that only in the women with pPROM was the frequency of allele 12 homozygosity decreased from women with term deliveries (P<.0001). The absence of the 12 repeat was more frequent in women who delivered at <32 weeks (18.4%), at 32-34 weeks (30.8%) and at 35-36 weeks (29.4%) as compared to women who delivered at >36 weeks (10.7%) (P<.05). The absence of the 12 repeat was also more frequent in women who delivered a low birth weight infant (23.5%) as compared to those who delivered an infant >2500 g (10.9%) (P=.02).

      Conclusion

      The absence of homozygosity for the 12 unit repeat in the CIAS1 gene coding for the NALP3-inflammasome is a risk factor for pPROM.