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UT-Houston's Northrup and Colleagues Uncover Genetic Link to Spina Bifida

December 19, 2007

Researchers at The University of Texas Medical School at Houston have discovered an association between genes regulating glucose metabolism and spina bifida. The decade-long study looked at more than 1,500 DNA samples from parents and their children with that birth defect.

UT Medical School researchers tested variants in a dozen genes that take part in glucose metabolism to look for a link between genetic variation in affected children and spina bifida. Each affected child's parents were also studied, as well as DNA from unaffected control samples. The samples were gathered from study participants in Houston, Los Angeles and Toronto.

Published in the Jan. 2008 issue of the journal Reproductive Sciences, the study titled "Genes in Glucose Metabolism and Association with Spina Bifida," found an association between variants in three glucose metabolism genes and spina bifida. Glucose metabolism is the way the body uses its major fuel, which is sugar.

"We are trying to find out what causes this neural tube defect. It has been recognized through epidemiological studies for a number of years that there was a connection between high glucose levels, either due to maternal diabetes or obesity and having a child with spina bifida," said co-author Hope Northrup, M.D., professor and director of medical genetics in the Department of Pediatrics at the UT Medical School. "Our goal is to identify variations in specific genes of glucose metabolism that are important in the process, thus enabling us to more specifically determine the underlying problem."

Spina bifida is the most common permanently disabling birth defect in the United States, according to the Spina Bifida Association. It happens when the spine of the baby fails to close during the first months of pregnancy. It occurs in seven out of 10,000 births in the United States. According to the Spina Bifida Association of Texas, a Hispanic woman is twice as likely to have a child with this crippling birth defect. In Texas, nearly two out of every 1,000 babies born have spina bifida.

Northrup said this study supports why women need to maintain a healthy weight throughout their childbearing years, and beyond.

"This is important from a practical standpoint because neural tube defects are more common in pregnancies complicated by maternal diabetes and maternal obesity, and our study suggests a mechanism for this association," said Manju Monga, M.D., professor and director of maternal and fetal medicine in the medical school's Department of Obstetrics, Gynecology and Reproductive Sciences. "In the United States, Mexican-American women have the highest rates of neural tube defects and they are also at increased risk for obesity and adult-onset diabetes, so this study may be especially relevant to pregnant women in Texas."

Another way women can reduce their risk of having a baby with spina bifida: take 400 micrograms of folic acid daily. The number of cases could be reduced by as much as 70 percent.

The lead author of the study is Christina Davidson, M.D., who was a fellow in the Department of Obstetrics, Gynecology and Reproductive Sciences at the UT Medical School. She currently is at Baylor College of Medicine.

Co-authors at the UT Medical School, along with Northrup, include: Terri M. King, Ph.D.; Kit Sing Au, Ph.D.; Irene Townsend, R.N. Others are: Jack M. Fletcher, Ph.D., University of Houston; and Gayle H. Tyerman, M.D., Shriners Hospital for Children, Los Angeles.

The study was funded with grants from the National Institutes of Health and Shriners Hospital for Children.

The University of Texas Medical School at Houston

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