Stroke Susceptibility Gene for Men Identified

Researchers at the University of Texas School of Public Health at Houston’s Human Genetics Center have identified a genetic variation that raises stroke risk among middle-aged men.

Writing in the March edition of Genetic Epidemiology, lead author Dr. Alanna Morrison and colleagues identify a variation in the lipoprotein lipase, or LPL, gene that raises a man’s risk of having a clinical stroke by 2.5 times. Having the variation, known as LPL S447X, poses a four-fold increase in the risk of having a subclinical stroke, also known as "silent stroke."

Heightened risk for men between 45 and 64 years of age was evident even after adjusting for other stroke-risk factors that could affect the connection between the gene and stroke risk. No statistically significant effect was found on stroke risk among women.

LPL plays a role in regulating cholesterol and triglycerides. The research team targeted genes known to regulate lipids, including high-density lipoprotein and low-density lipoprotein, also known as "good" and "bad" cholesterol, respectively. The association of these genes with lipids and atherosclerosis made them candidate genes for stroke.

LPL S447X is characterized by a single change in the genetic code at one spot on the gene. That minute change, however, shortens the LPL protein that the gene creates by deleting two amino acids that usually constitute part of the protein.

"This variation has a dramatic effect on the protein," Dr. Morrison noted.

Researchers hypothesize that the difference in effect between the sexes could be attributed to gender differences in LPL activity or to differences in hormonal regulation of metabolic processes among men and women.

The study of 1,579 individuals from 15,794 middle-aged people enrolled in the Atherosclerosis Risk in Communities study provides a basis for further exploring the connection between the LPL variation and stroke.

Further understanding how the LPL S447X contributes to stroke risk will be useful for potential early identification of people at increased risk for stroke, senior author Dr. Eric Boerwinkle noted.

The LPL variation is the second stroke susceptibility gene identified by Human Genetics Center researchers. Morrison was lead author and Dr. Boerwinkle senior author of a paper identifying the G protein Beta 3 subunit as a stroke-susceptibility gene published last April in Stroke, a journal of the American Heart Association.

Co-authors of the LPL paper are Drs. Molly Bray, assistant professor of biological sciences at the Human Genetics Center; Christie M. Ballantyne, Baylor College of Medicine’s Department of Medicine; Lloyd E. Chambless, University of North Carolina’s Biostatistics Department; and A. Richey Sharrett, National Heart, Lung, and Blood Institute.

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©2006 Texas Medical Center

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