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Gene Variant Increases Risk of Miscarriage among Hutterites
By Nancy Touchette

Researchers have identified a new gene variant that increases the risk of miscarriage. The gene was found in the Hutterite population of South Dakota, but it is likely to occur in the general population as well.

The Hutterites are a religious sect, much like the Amish of Pennsylvania, that originated in the Tyrolean Alps in the 1500s and migrated to South Dakota in the 1800s. They were chosen for the study because they are descended from a small number of founding ancestors and their genealogy is well documented.

The gene, known as HLA-G, codes for a protein that helps the body recognize foreign invaders. Most HLA proteins occur in cells throughout the body, but HLA-G is unusual because it is found primarily in the fetal placenta.

The gene variant, called –725C/G, occurred in 16 percent of the individuals studied. When two copies of the variant were inherited by the fetus, the risk of miscarriage was 28 percent, compared with 17 percent when one copy was present and only 10 percent when the variant was absent.

Miscarriage occurs in about 15 percent of all pregnancies, making it the most common disorder in pregnancy. It is usually caused by gross abnormalities in the chromosomes of the fetus—but not always. The causes of many miscarriages are unexplained.

The new study, conducted by Carole Ober and her colleagues at the University of Chicago, suggests that the variant reduces the amount of HLA-G protein produced by the fetus. Without the protein, the placenta may be subject to attack by maternal immune cells.

Other HLA-G variants have previously been implicated in miscarriage. The current study, published in the American Journal of Human Genetics, identifies 13 new HLA-G variants, but only –725C/G appears to affect pregnancy.

—Related Links—

Riverview Hutterite Colony School

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Ober, C. et al. Variation in the HLA-G promoter region influences miscarriage rates. American Journal of Human Genetics 72, 1425-1435 (June 2003).

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