SMFM: Gene Variants Linked to Preterm Labor (CME/CE)

Genetic variants involved in regulating inflammation and the extracellular matrix may increase the risk of preterm birth, researchers say.

A single nucleotide polymorphism (SNP) in fetal interleukein-6 (ILR6) and another in maternal tissue inhibitor of metalloproteinase 2 (TIMP2) were each associated with a two-fold increased risk of spontaneous preterm birth.

Roberto Romero, MD, of the National Institute of Child Health and Human Development, and colleagues reported the findings at the Society for Maternal-Fetal Medicine meeting in Chicago.

“The genetic makeup of both mother and fetus can contribute to the risk of premature labor,” Romero told MedPage Today. “Our discovery … helps explain why some mothers have premature labor and delivery despite having optimal prenatal care.”

Inflammatory hormones have been shown to play a role in the labor process, and previous studies have found that a third of preterm infants are born to mothers with a silent amniotic infection.

Now, the findings suggest that individual genetic variation involved in that inflammatory response may account for discrepancies in preterm births.

“We have a large body of evidence that proves silent infections are a frequent and important cause of premature labor,” Romero said. “These infections can also attack the fetus before it is born.”

He explained that the mother’s hormones initiate the onset of labor to get rid of the infected tissue, and the fetus seeks to exit a hostile intrauterine environment that threatens its survival.

To look at the mechanisms by which this process occurs, Romero and colleagues conducted a case-control study of mothers in Chile to assess genetic factors that could predispose women to spontaneous preterm labor and delivery.

Patients who delivered prior to 37 weeks gestation served as cases, while women who delivered a normal neonate at term served as controls. There were 223 mothers and 179 fetuses in the case group, and 599 mothers and 628 fetuses in the control group.

The researchers subsequently examined 190 candidate genes and 775 SNPs.

They found that the strongest fetal single-locus association with risk of spontaneous preterm birth was in ILR6, (OR 2.07, 95% CI 1.42 to 3.02, P=0.0001).

The strongest maternal single-locus association with spontaneous preterm labor and delivery was in tissue inhibitor of metalloproteinase TIMP2 (OR 1.98, 95% CI 1.38 to 2.83, P=0.0002). This gene is involved in regulating the extracellular matrix, which holds cells within tissues.

The associations remained significant after controlling for multiple comparisons, Romero said.

Global haplotype analysis also indicated an association between a fetal DNA variant in insulin-like growth factor 2 (P=0.004) as well as maternal alpha 3 type IV collagen isoform 1 (COL4A3) (P=0.007).

“Some women and fetuses carry gene variants that predispose them to the early onset of labor,” Romero said.

The researchers reported no conflicts of interest.

source : www.medpagetoday.com

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