In Hispanic Women, Genetic Variations Linked To Spontaneous Preterm Birth

Preterm birth is a major cause of illness and death in newborns. A genetic cause of preterm birth was suggested by racial disparity, a tendency to occur within families and a high rate of recurrence, according to Errol Norwitz, M.D., associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale and lead investigator of the study.

Norwitz and his team prepared DNA samples from 102 mothers with a spontaneous unexplained preterm birth and 408 mothers who delivered at term with no complications. They then compared the distribution of 128 well-known genetic variations, known as single nucleotide polymorphisms, in 77 genes between the two groups. The patients in the study were identified from the March of Dimes Perinatal Epidemiology Research Initiative Project at Yale and New York University between January 1989 and June 2005.

"Our analysis demonstrates that, in an Hispanic population, mothers who carried any one of four polymorphisms were significantly more likely to have a spontaneous preterm birth," said Norwitz.

The four polymorphisms included CYP2C9S144, IL6S174, CCR5S1 and ENPP1S121. The risk of preterm birth was highest among women with the ENPP1 variant.

"The strong association of ENPP1 was particularly compelling, but how this variant functions and why it predisposes preterm births still needs to be determined," said Norwitz.

In another abstract using the same study subjects, Norwitz and colleagues explored whether polymorphisms in the gene that encodes the progesterone receptor may identify women at risk for preterm birth. The team found no such association.

"Progesterone supplementation may prevent preterm birth in about 30 to 40 percent of women at high risk by virtue of a prior preterm birth, but exactly how progesterone supplementation works is still unknown," said Norwitz. "While this was a negative finding, it was an important question to answer."

Other authors on both abstracts included Thomas Morgan, Victoria Snegovskikh, Edward Kuczynski, Hee Joong Lee, Frederick Schatz, Se-Te Joseph Huang, Catalin Buhimschi, Edmund Funai, Irina Buhimschi, Antonette Dulay, Guoyang Luo, Sonya Abdel-Razeq and Charles Lockwood.

Abstract #297: "Identification of Single Nucleotide Polymorphisms in Maternal Genes Associated with Spontaneous Preterm Birth."

Abstract # 316: "Single Nucleotide Polymorphisms in the Human Progesterone Receptor (PR) Gene and Spontaneous Preterm Birth."