Overall, those with at least one copy of KL-VS had approximately twice the risk of having atherosclerosis than others. Start adding known risk factors to the presence of KL-VS, and risk really shot up, the researchers discovered.
For example, smokers with at least one KL-VS copy had more than seven times the risk of non-smokers without the gene variant. Smokers who had low (less than 40 mg/dl) "good" cholesterol, or HDL, and at least one copy of KL-VS had about 10 times the risk of comparable individuals without the variant. However, high levels of "good" cholesterol, known as HDL, significantly reduced the risk associated with the KL-VS variant.
"What is particularly exciting," says Arking, "is that we have demonstrated that modifiable risk factors, including hypertension, smoking and HDL cholesterol levels, can modulate the risk imposed by KL-VS."
How exactly klotho increases the risk of atherosclerosis, or exacerbates the effects of smoking, is still unknown. The klotho gene carries the blueprint for a protein that seems related to enzymes known as beta-glycosidases, but no specific target for the klotho protein has been identified. The KL-VS gene results in two changes in the protein's sequence that seem to influence how cells secrete the protein and how well it functions, say the researchers.
The work was funded by the Howard Hughes Medical Institute, the National Institutes of Health and The Johns Hopkins University School of Medicine General Clinical Research Center.
Authors on the report are Arking, Dietz, Diane Becker, Lisa Yanek, Daniel Judge, Taryn Moy and Lewis Becker, all of the Johns Hopkins School of Medicine; and Daniele Fallin of the Johns Hopkins Bloomberg School of Public Health.
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
1-May-2003