Hypertension: High Resolution
Array Analyses Reveal the Risk in
Williams Syndrome is Determined
by Gender and Parent of Origin
-
1
Cedars-Sinai Medical Center at UCLA, Departments of Pediatrics and Medical Genetics Institute, United States
-
2
The Children's Hospital of Philadelphia, United States
Hypertension (HTN) is the leading independent risk factor for stroke and cardiovascular disease. Despite intensive study, the genetic origins of essential hypertension are largely unknown although it accounts for more than 95% of cases. We have combined high resolution SNP array analyses with phenotypic analyses of WS and report that the elevated risk of HTN in Williams Syndrome (WS) is significantly modified by both gender and parental origin of the deletion and that the size of the deletion does not correlate with the risk. We initially determined the parental origin of the deletion and HTN in 53 families with WS (ages 12- 51y) and 32% reported HTN. We found HTN in 21% (6/29) of those with maternally derived deletions in contrast to 46% (11/24) of those with paternally derived deletions. To better model the HTN risk factors found in the normal population, we reasoned that gender might also affect the risk of HTN in WS, independent of parental origin of the deletion. Unexpectedly, we found a highly significant effect in females with 0% (0/17) HTN in those with maternally derived deletions vs 40% (6/15) in those with paternally derived deletions. In contrast, males had an increased risk of HTN regardless of the parental origin of the deletion with HTN found in 56% (5/9) with paternally derived and 50% (6/12) with maternally derived deletions. To test the significance of these findings, we examined a second independent population of 30 WS families and observed a similar trend: in females, only 10% (1/10) of maternal but 29% (2/7) of paternal deletions had HTN in contrast to 67% (2/3) of paternal and 40% (4/10) of maternal males. Molecular extent of the deletion was measured by using the 1M Illumina SNP array. Combining both populations in a multivariate model, we find that the risk of HTN is independently related to gender (p=0.0002), age (p=0.0002), and parental origin of the deletion (p=0.0107). In summary, the risk of HTN appears to be dramatically affected by gender and the parental origin of the deletion in WS. This suggests an imprinted gene(s) in the WS region affecting HTN as well as a potential role for gender specific epigenetic imprinting in HTN. We propose that incorporating this in current models may improve the ability to define genes for essential HTN in the normal population.
Conference:
12th International Professional Conference on Williams Syndrome, Garden Grove,CA, United States, 13 Jul - 14 Jul, 2008.
Presentation Type:
Poster Presentation
Topic:
Multidisciplinary Poster Session
Citation:
Gao
MC,
Wijesuriya
H,
Dai
L,
Appelbaum
M,
Chen
XN,
Simon
A and
Korenberg
JR
(2009). Hypertension: High Resolution
Array Analyses Reveal the Risk in
Williams Syndrome is Determined
by Gender and Parent of Origin.
Conference Abstract:
12th International Professional Conference on Williams Syndrome.
doi: 10.3389/conf.neuro.09.2009.07.037
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
04 May 2009;
Published Online:
04 May 2009.
*
Correspondence:
M. C Gao, Cedars-Sinai Medical Center at UCLA, Departments of Pediatrics and Medical Genetics Institute, Los Angeles, United States, mgao@ucla.edu