THURSDAY, March 15, 2007 (HealthDay News) -- Variations in two of a patient's genes may dictate whether or not a hip replacement will fail them over the following 10 years, new research shows.

"I don't think that there will be any immediate changes in our surgical practice, but eventually such genetic factors will have to be taken into account in our surgical planning," said Dr. Samuel J. Chmell, an associate professor in the department of orthopedic surgery at the University of Illinois in Chicago.

Chmell was not involved in the study, which is published in the March 15 issue of the Annals of Rheumatic Diseases.

According to the study's British authors, mutations in the matrix metalloproteinase 1 (MMP1) gene and variations in the vitamin D receptor gene significantly increase the risk that a hip replacement will fail in the decade following surgery.

Knowing who has the genetic variation may help doctors predict which patients are likely to have serious problems after hip replacement surgery, lead researcher Dr. Hammad Malik, from the Centre for Integrated Genomic Medical Research at the University of Manchester and colleagues noted.

His team found that patients with variations in MMP1 are more than three times as likely to have aseptic loosening, a condition in which the artificial joint comes loose and the surrounding bone begins to dissolve, compared with those who did not have the variation.

Malik's group also found that patients with variations in the vitamin D receptor gene were almost two times more likely to encounter bone dissolution and deep infection.

"There are unknown biological factors involved in these problems," said Dr. Mark H. Gonzalez, a professor of orthopedic surgery at the University of Illinois at Chicago who was not involved in the study. "This study shows an association between aseptic loosening and MMP1. This is a very interesting association, and an understanding of this association may allow us to identify patients who are at risk for aseptic loosening."

The finding may also help in the choice of prosthetic materials -- metal on polyethylene, metal on metal or ceramic on ceramic, Gonzalez said. "It may also allow us to proactively intervene pharmacologically to treat at-risk patients," he added.

In the study, the researchers analyzed genetic variations in 312 people who underwent hip replacement surgery. Among these patients, 162 had problems with their hip replacement during the 10 years after the procedure.

Ninety-one had early signs of aseptic loosening and 71 developed a deep-seated infection. This type of infections happens when the body can't fight infection from bacteria living within an artificial implant.

To look for the genetic causes of these problems, the researchers took DNA samples from all the patients and tested for genetic variations in the MMP1 gene, the interleukin 6 gene, and the vitamin D receptor genes.

MMP1 is an enzyme that degrades collagen, a protein found in bone and cartilage. Interleukin 6 is a chemical associated with bone metabolism and the immune response, and vitamin D synthesis is needed for strong healthy bones.

Malik's group found that variations in the interleukin 6 gene did not have any effect. However, patients with variations in MMP1 were more than three times more likely to have aseptic loosening. Moreover, variations in the vitamin D receptor gene increased the chances of bone dissolution and deep infection.

"The findings of this study are consistent with and supportive of our present clinical observations," Chmell said.

If the findings are confirmed, they could be used to predict long-term success of hip replacement surgery. They could also be used to develop new targeted genetic treatments, Malik's team concluded.

More information

For more on hip replacement, visit the U.S. National Institutes of Health.

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