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Genetic makeup may affect HRT, heart disease risk

by Ross Tomlin

Paul F. Bray, MD

From soybeans to hormones, remedies for women suffering postmenopausal ailments run the gamut of numerous unproven treatments, some of which can do more harm than good.

A study on blood clotting at Baylor College of Medicine appears to have resolved some of the confusion, showing that genetic variations may affect the chances of heart attacks in women using hormone replacement therapy.

Paul F. Bray, MD, professor of medicine and chief of thrombosis research at BCM, and his colleagues found that hormone replacement therapy affects patients differently, depending on their genetic makeup. The study, funded by the National Institutes of Health, investigated whether inherited variations in blood clotting genes are risk factors for coronary heart disease in postmenopausal women.

"The end goal is to be able to predict who might and might not be at risk for side effects from hormone therapy," said Bray. "Because we were particularly interested in the side effects related to arterial disease, we were focusing on genes that are involved in blood clot formation as well as genes that are involved in platelet biology and platelet function. If our findings were to hold up in other studies, we could use this kind of genetic information to predict who might be safe from some outcomes but be at risk for others."

Genotypes analyzed

Bray and researchers at Wake Forest University School of Medicine and the University of California at San Francisco analyzed the genotypes of women who had participated in the 1998 Heart and Estrogen-progestin Replacement Study, which showed that women in the first year of the study had 53 percent more heart attacks than study participants not taking HRT. The increased risk decreased over the following years of the study, however, prompting Bray to take a closer look at the link between HRT and heart attacks.

Of 2,145 HERS patient samples analyzed by Bray and his associates, 537 belonged to women who had suffered fatal or non-fatal heart attacks or had developed unstable angina. Seven genes were studied based on their roles in clot formation. (Clot formation can lead to a heart attack.)

Two of the genes – both crucial in the early stages of clot development – were found to react differently to hormone therapy. Depending upon which form of the gene was inherited, the risk of heart disease was either increased or decreased.

"Furthermore, the risk associated with hormone therapy was even greater with combinations of these gene variations," Bray said.

Although Bray's study provides a better understanding of the correlation between genes and hormones in instances of coronary heart disease, other purported side effects of HRT – such as a decreased risk of osteoporosis and increased risks of breast cancer and stroke – must be studied further.

Until then, Bray says, medical experts will not know, for instance, whether certain genes play dual roles in reducing the chances of one health problem while raising the odds of another.

Findings presented

In December, Bray presented his team's findings at the American Society of Hematology's annual meeting in San Diego. The four-day conference, which focused on blood disease and cancer research, featured approximately 200 abstracts for oral presentation out of several thousand submitted. ASH, a non-profit organization with more than 13,000 members, is the world's largest professional society concerned with the causes and treatment of blood disorders.

"We were one of the best-received abstracts in the clinical thrombosis session, so I think it caught some people's attention," Bray said.

Although the study's abstract has been publicized, more analysis remains before a final report on the study will be published. Bray and his colleagues will follow up on their work heretofore by performing a similar study using a different population of patients, which will be supplied through the Women's Health Initiative, a large-scale research initiative comprising 90,000 study participants.

"Confirming our findings in a separate population is very important for these kinds of studies," Bray said. "There is a lot of literature out there that doesn't necessarily hold up, but I think this study is pretty exciting from the perspective that it has the potential to impact millions of women's lives.

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