Document Detail

24-h ambulatory blood pressure is linked to chromosome 18q21-22 and genetic variation of NEDD4L associates with cross-sectional and longitudinal blood pressure in Swedes.
MedLine Citation:
PMID:  16788695     Owner:  NLM     Status:  MEDLINE    
Numerous linkage studies have indicated chromosome 18q21-22 as a locus of importance for blood pressure regulation. This locus harbors the neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) gene, which is instrumental for the regulation of the amiloride-sensitive epithelial sodium channel (ENaC). In a linkage study of 16 markers (including two single nucleotide polymorphism markers located within the NEDD4L gene) on chromosome 18 between 70-104 cM and ambulatory blood pressure (ABP), in 118 families, the strongest evidence of linkage was found for 24 h and day-time systolic ABP at the NEDD4L locus (82.25 cM) (P=0.0014). In a large population sample (n=4001), we subsequently showed that a NEDD4L gene variant (rs4149601), which by alternative splicing leads to varying expression of a functionally crucial C2 domain, was associated with diastolic blood pressure (DBP) (P=0.03) and DBP progression over time (P=0.04). A genotype combination of the rs4149601 and an intronic NEDD4L marker (rs2288774) was associated with systolic blood pressure (SBP) (P=0.01), DBP (P=0.04), and progression of both SBP (P=0.03) and DBP (P=0.05) over time. A quantitative transmission disequilibrium test in the family material of the rs4149601 supported this NEDD4L variant as being at least partially causative of the linkage result. In conclusion, our findings suggest that the chromosome 18 linkage peak at 82.25 cM is explained by genetic NEDD4L variation affecting cross-sectional and longitudinal blood pressure, possibly as a consequence of altered NEDD4L interaction with ENaC.
C Fava; F von Wowern; G Berglund; J Carlson; B Hedblad; L Rosberg; P Burri; P Almgren; O Melander
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-06-21
Journal Detail:
Title:  Kidney international     Volume:  70     ISSN:  0085-2538     ISO Abbreviation:  Kidney Int.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-07-27     Completed Date:  2006-11-30     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  562-9     Citation Subset:  IM    
Department of Clinical Sciences, University Hospital MAS, Malmö, Sweden.
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MeSH Terms
Alternative Splicing
Antihypertensive Agents / therapeutic use
Blood Pressure / genetics*
Blood Pressure Monitoring, Ambulatory
Chromosomes, Human, Pair 18*
Circadian Rhythm*
Cross-Sectional Studies
Endosomal Sorting Complexes Required for Transport
Genetic Predisposition to Disease / epidemiology
Genetic Variation
Hypertension / drug therapy,  epidemiology,  genetics*
Insulin / blood
Linkage (Genetics)
Longitudinal Studies
Middle Aged
Polymorphism, Single Nucleotide
Risk Factors
Sweden / epidemiology
Ubiquitin-Protein Ligases / genetics*
Reg. No./Substance:
0/Antihypertensive Agents; 0/Endosomal Sorting Complexes Required for Transport; 11061-68-0/Insulin; EC ubiquitin protein ligases; EC Ligases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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