Male Fat Distribution Pattern & Coronary Risk Profile Linked to X Chromosome

Women Lacking Ovarian Function Shy, Anxious

Two risk factors that place males at greater risk for heart disease than women appear to be influenced by genes on the X chromosome, report researchers at the NIH and the University of Texas Southwestern Medical School. The finding appears in a Research Letter in the Journal of the American Medical Association.

In a separate Research Letter, the researchers at the NIH and at Thomas Jefferson University in Philadelphia also report that women who lack functioning ovaries—either because of a hereditary condition or due to an illness—are more likely than are other women to experience shyness and anxiety in social situations.

In the first report, researchers studied women with Turner syndrome, a hereditary condition in which women are missing all or part of one X chromosome, explained the senior author of both reports, Carolyn Bondy, Chief of the Developmental Endocrinology Branch at NIH's National Institute of Child Health and Human Development.

The researchers tested whether the women had inherited their single normal X chromosome from their mothers or from their fathers. Women normally inherit one of their two X chromosomes from their mother and one from their father. Men normally inherit a single X chromosome from their mothers.

The researchers also measured the women's body fat distribution patterns and their cholesterol and triglyceride levels. Dr. Bondy explained that men have a greater tendency than do women to accumulate fat within their abdomens, while women tend to accumulate fat around their hips, buttocks, and thighs. Proportionally higher abdominal fat distribution is associated with cholesterol levels that increase the chances of cardiovascular disease.

The researchers found that the women with Turner syndrome who had inherited their X chromosome from their mothers were more likely to accumulate abdominal fat and to have cholesterol patterns associated with cardiovascular disease than were women who had inherited their X chromosomes from their fathers. The differences in fat distribution and cholesterol patterns between the two groups of women in the study paralleled the differences normally observed between men and women, the researchers wrote.

Dr. Bondy explained that in women with two X chromosomes, only 1 X chromosome functions in any given cell of the body. In roughly 50 percent of the cells, only the X chromosome inherited from the mother is functioning, and in the other 50 percent, only the X chromosome inherited from the father is functioning.

In the paper, the researchers theorize that certain genes—not yet discovered—on the X chromosome might protect against abdominal fat distribution and unhealthy cholesterol patterns. When inherited from the mother, these genes may be imprinted, or "switched off," so that they no longer function. Because most women have functioning X chromosomes from their fathers, they may have functioning copies of genes that protected against abdominal fat accumulation and unhealthy cholesterol patterns. But because most males inherit only one X chromosome from their mothers, they aren't protected.

"These novel observations indicate that X-chromosome genes may be involved in coronary artery disease susceptibility and as such have broad implications for public health," Dr. Bondy said.

For the second report, the researchers studied women with Turner syndrome and women with premature ovarian failure, or POF. With POF, the ovaries cease to function, and women enter a menopause-like condition years before menopause naturally occurs. In Turner syndrome, the ovaries usually do not function. Women with these conditions are usually sterile.

The researchers administered measures of psychological and social function to both groups of women as well as to women with normally functioning ovaries. They found that both the women with Turner syndrome and the women with POF were more likely than women with normal ovarian function to report feelings of anxiety in social situations, shyness, depression, and low self esteem.

The study authors suggested that, when evaluating young women with ovarian failure, physicians and other care givers should consider that the women also may need help in dealing with these feelings.


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