Study Says Gene Linked To Pregnancy Disorder

Doctors, including one working at Harvard's Brigham and Women's Hospital, may have found a genetic mutation responsible for dangerous increases in blood pressure observed in more than one in 20 pregnant women, a new study reports.

Researchers published findings in Saturday's issue of Nature Genetics of a correlation between a gene mutation and the condition known as preeclampsia, which most often strikes women in their first pregnancy.

Jean-Mark Lalouel, a co-author of the study and professor of human genetics at the University of Utah, last week called the findings only a first step, saying the gene defect may eventually aid in early diagnosis and treatment.

Toxemia, as the condition is more commonly known, is the forerunner of eclampsia, in which women fall victim to convulsive seizures near the end of pregnancy. Left untreated, such seizures can lead to death in preeclampsia's victims, who are usually very young mothers or older mothers aged 35 to 40.

Lalouel and other researchers, including Medical School Assistant Professor of Medicine Dr. Richard P. Lifton, examined DNA of women in Utah and Japan who had been diagnosed with preeclampsia. The mutation the study found lies in the gene coding for angiotensinogen, a protein involved in regulating blood pressure.

The finding is significant because a common diagnosis of preeclampsia is an increase in blood pressure, or hypertension, and the presence of excess protein in the urine.

Pregnancy brings about major physiological changes and it is possible that these changes reveal "the underlying differences" between those who develop preeclampsia and those who do not, Lalouel said, among those who inherit the preeclampsia genetic defect.

Among physicians who treat pregnant women, definitions play a crucial role in the debate over the causes of hypertension.

"No one is satisfied with the definition [of preeclampsia itself]," Lalouel said, which often makes it difficult to make positive diagnoses of preeclampsis.

Gordon H. Williams '59, professor of medicine at the Medical School, cautioned against drawing too many conclusions from the finding since it is a "retrospective study, which always has its limitations."

Williams, who co-authored a commentary in the same issue of Nature Genetics on the meaning of the study, pointed out that this was an "association study" and does not prove conclusive or direct linkage between the mutation and the disorder.

"[This study] provides the first potential example of a specific gene which may be--and may be is in big words--associated with preeclampsia," Williams said.

But some questions remain, according to Williams. Last year, the same research group demonstrated an association of the same gene defect with normal hypertension. Why, he asked, are preeclamptic women not prone to develop normal hypertension later in life?

First Pregnancy May Leessen Risk

Lalouel suggested that the first pregnancy may somehow eliminate the risk factor, but he acknowledged that not enough information has been accumulated to test this hypothesis.

Lalouel said that six studies, including one by a team in Scotland, confirm the group's results. Lalouel said a prospective study is in th

Gordon H. Williams '59, professor of medicine at the Medical School, cautioned against drawing too many conclusions from the finding since it is a "retrospective study, which always has its limitations."

Williams, who co-authored a commentary in the same issue of Nature Genetics on the meaning of the study, pointed out that this was an "association study" and does not prove conclusive or direct linkage between the mutation and the disorder.

"[This study] provides the first potential example of a specific gene which may be--and may be is in big words--associated with preeclampsia," Williams said.

But some questions remain, according to Williams. Last year, the same research group demonstrated an association of the same gene defect with normal hypertension. Why, he asked, are preeclamptic women not prone to develop normal hypertension later in life?

First Pregnancy May Leessen Risk

Lalouel suggested that the first pregnancy may somehow eliminate the risk factor, but he acknowledged that not enough information has been accumulated to test this hypothesis.

Lalouel said that six studies, including one by a team in Scotland, confirm the group's results. Lalouel said a prospective study is in th