Nature and the Nature research journals press release

A new study published in the April issue of Nature Genetics provides a predictive model that can identify sickle cell anemia (SCA) patients at risk of stroke with greater accuracy and faster than current methods allow, which may be useful as a prognostic test. Stroke is a major risk factor for sickle cell anemia patients under 20 years of age.

Paola Sebastiani, Marco Ramoni and colleagues analyzed 235 variations in 80 candidate genes in 1,398 sickle cell anemia patients, in order to develop a model that captured the genetic and clinical factors that influenced the risk of stroke. The authors validated the model in an independent population of 114 subjects, correctly predicting the occurrence of stroke with 98.2% accuracy. The analysis found that 25 variations within 11 genes, combined with 4 clinical variables, interact to significantly influence the risk of stroke. These include some factors previously associated with stroke in the general population, including 3 genes in the TGF-beta pathway as well as hemoglobin levels. This provides evidence that stroke risk is a complex trait with multiple genetic and clinical influences, and suggests candidates that may be important in predicting stroke risk in the general population.

Currently, Transcranial Doppler (TCD) flow studies are used to predict the likelihood of stroke in children and young adults with SCA. However, the usefulness of this as a predictive test is limited, as only 10% of cases with abnormal TCD values will have a stroke, while some individuals with normal values will have a stroke.

Author Contact:

Marco Ramoni
(Harvard Medical School, Boston, MA, USA)
Tel: +1 617 525 4466, Cell: +1 617 823 7468, Email: marco_ramoni@harvard.edu

Paola Sebastiani
(Boston University School of Public Health, Boston, MA, USA)
Tel: +1 617 638 5877, Email: sebas@bu.edu

Other papers from Nature Genetics to be published online at the same time and with the same embargo:

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[4] Wnt signals two ways to a healthy gut

DOI: 10.1038/ncb1240

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The Wnt signalling system is known to control the turnover of cells in the gut, and over-activation of this system leads to intestinal tumours. The new findings from Dr. Hans Clevers and colleagues bring a note of caution for cancer therapies aimed at blocking Wnt signalling because this could also adversely affect the availability of these bacterial defence cells.

Wnt signals are known to be necessary for maintaining a pool of undifferentiated intestinal progenitor cells, which can replenish all the different cell types of the intestine in response to injury among other things. This new study shows that Wnt signals also control both the maturation and the correct positioning of a specific type of intestine cell -- the Paneth cell --which is known to be important for secreting anti-bacterial peptides.

This dual role of Wnt -- maintaining a progenitor cell while also inducing a mature cell -- is demonstrated by the observation that intestinal tumour cells, resulting from overproduction of the progenitor cells, also show some molecular characteristics of mature Paneth cells.

Author contact:

Dr. Hans Clevers
(Netherlands Institute for Developmental Biology, Utrecht, The Netherlands)
Tel: +31 302121826, Email: clevers@niob.knaw.nl

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Nature and the Nature research journals press release