Posted May 21, 2009
From Danny Devito to Yao Ming, the world is filled with short people and tall people and everyone in between. While factors such as nutrition influence height differences, much of that variation depends on genes. After all, both of Ming’s parents were basketball stars, and Devito’s were not.
But the genes that made Ming grow to 7 feet 6 inches and Devito stop growing several feet shorter could be important for more than sports. Changes in how height genes work could not only add or subtract a few centimeters from leg length, but could also affect underlying cell biology in ways that can lead to disease, recent research suggests.
Statistical studies find that shorter people are more likely to get heart disease, diabetes and osteoarthritis. Other studies show that the same genes that make healthy cells multiply to make a person grow taller can also make cancer cells proliferate in tumors. On the other hand, genes that make bones grow longer can form extra cartilage in joints, protecting them from the ravages of osteoarthritis.
The long and short of it is that height genes might affect health as well as height – although scientists don’t completely understand how.
Some genes that have been implicated in determining height have been well studied for their connections to particular diseases, but not as well-studied for how they affect height. And while statistical links between height and disease are robustly documented, scientists don’t completely understand if or how the same genes could set the foundation for both height and disease.
Pinning down that connection could have payoffs for treating disease and ensuring health.
“When you take a kid to the pediatrician, the first thing they do is measure the child’s height,” says geneticist Guillaume Lettre of Children’s Hospital Boston and of the Broad Institute, in Cambridge, Mass. He is coauthor of a study that identified several genes associated with height.
Growing too fast or too slow could bea sign of health problems such as hormone imbalances. But if the genes controlling height were well known, pediatricians could easily determine whether a short-for-their-age child simply inherited the gene variants that denote a more diminutive stature, or actually has a more serious condition, Lettre says.
Linking height genes to health is difficult, though, because details of the genetic pathway to height are complex. Many genes work together to create normal variations in height. So far, the suspicion that height genes affect health is supported mostly by statistical studies.
In 2001, for instance, epidemiologist David Gunnell of the University of Bristol in England and colleagues found that taller people can face a 20 to 60 percent greater risk for various cancers, including of the breast, prostate and colon.
Last year, epidemiologist Luisa Zuccolo, also of Bristol, followed up on Gunnell’s work with a study focused on the link between height and prostate cancer. The risk of developing prostate cancer increased by 6 percent for every 10 centimeters over the median height of the 1,357 men in the study, Zuccolo and colleagues reported in Cancer Epidemiology, Biomarkers & Prevention. Despite the link, height was still less of a risk factor than age and family history, but “understanding why height is associated with prostate cancer could help us to understand its causes,” Zuccolo says.
One molecule that taller people have in abundance compared with shorter people is insulin-like growth factor 1, or IGF-I. The insulin-like molecule stimulates the growth of cells and tissues, and higher levels of the molecule have also been linked to the incidence and progression of several different types of cancer. IGF-I can bind to the tumors of cancers of the breast, prostate and bladder, stimulating the growth of tumor cells. Zuccolo speculates that the IGF-1 gene could link height and prostate cancer.
Stimulating growth
IGF-1 is a protein that binds to receptor molecules on other cells, triggering a cascade of events that eventually stimulate cell growth.
A study reported in 2007 in Science found that variations in the IGF-1 gene were one reason that Chihuahuas don’t grow as large as Great Danes. Geneticist Nathan Sutler, then at the National Human Genome Research Institute in Bethesda, Md., and colleagues found that small dog breeds had one particular variant of the gene for IGF-1, but almost all giant breeds had a different version of the gene.
A 1993 study by Michael Ranke and colleagues at University Children’s Hospital in T
