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Researchers identify 5 genetic variations associated with risk of venous thrombosis in women

The JAMA Network Journals

Researchers have identified new genetic variations that may be associated with the risk of developing nonfatal venous thrombosis in postmenopausal women, according to a study in the February 7 issue of JAMA.

Deep vein thrombosis (blood clots in the thigh or leg) and pulmonary embolism (blood clots in the arteries leading to the lungs) cause significant illness and death in adult women, according to the background information in the article. The authors note that despite improved preventive treatments in high-risk patients, the incidence of venous thrombosis (VT) has not decreased.

In this study, Nicholas L. Smith, Ph.D., M.P.H., from the University of Washington, Seattle, and colleagues examined the association of common genetic variation in 24 clotting-related candidate genes with the risk of first-time VT in postmenopausal women. Study participants were 349 perimenopausal and postmenopausal women 30 to 89 years of age who sustained a first VT event between January 1995 and December 2002. The control group of 1,680 women included perimenopausal and postmenopausal women of the same age range who had no prior history of deep vein thrombosis or pulmonary embolism. Through blood samples taken from the study participants, the researchers analyzed genetic markers called haplotypes and changes in the DNA sequence called single nucelotide polymorphisms (SNP).

"Only the tissue factor pathway inhibitor gene demonstrated global association with risk. Five significant SNP associations were identified across three of the candidate genes (factors V, XI and protein C) in SNP analyses," the researchers report. Two of those associations had been previously reported. The researchers note that another 22 variants across 15 genes were also identified and classify them as "interesting associations."

"After accounting for multiple testing, five SNPs associated with VT risk were identified, three of which have not been previously reported. Replication of these novel associations in other populations is necessary to corroborate these findings and identify which genetic factors may influence VT risk in postmenopausal women," the authors conclude.


(JAMA. 2007;297:489-498. Available pre-embargo to the media at

Editor's Note: Co-author Dr. Psaty has reported receiving a speaker's honorarium from Celera Diagnostics. No other authors reported financial disclosures. This study was supported by National Heart, Lung, and Blood Institute grants and by a National Institute on Aging grant. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Separating Gold from Fool's Gold

"The completion of the human genome sequence has been accompanied by the rapid appearance of genetic association studies using large numbers of genetic markers to search for genetic variation underlying common, major health problems such as cardiovascular disease and cancer," write Josée Dupuis, Ph.D., and Christopher J. O'Donnell, M.D., M.P.H., in a related JAMA editorial.

"Physicians will increasingly encounter articles in the literature analyzing screens of ever-larger numbers of common genetic markers. An excellent example is the study of 280 single nucleotide polymorphisms (SNPs) in 24 venous thrombosis candidate genes reported by Smith and colleagues in this issue of JAMA.

"Like prospectors in the days of the gold rush, genetics researchers have entered an exciting era in which genome sequence information for humans and many other species is now fully available for use in large-scale association studies."

"Studies that are well-designed, appropriately analyzed and cautiously interpreted, such as the report by Smith et al, will confirm some findings and generate other new hypotheses. Replication in large, independent samples, as well as the determination of function significance, will be required to ultimately translate genetic variants into personalized genetic medicine."

(JAMA. 2007; 297:529-531. Available pre-embargo to the media at

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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