The non-synonymous polymorphism at position 114 of the WRN protein affects cholesterol efflux in vitro and correlates with cholesterol levels in vivo.

[werner syndrome]

Werner syndrome (WS ) is a recessive disorder characterized by the premature onset of a number of age-related diseases . The objective of the present study was to examine the degree of associations between non-synonymous coding Single Nucleotide Polymorphisms (SNPs ) in the WRN gene and markers of obesity , diabetes , and hypertension using meta -analyses publically available and to test their effect in WS fibroblasts . The P-value , after genomic control correction , for each non-synonymous coding SNP present in the WRN gene was retrieved from the International Consortium for Blood Pressure Genome-Wide Association Study , the Genome Wide Associations Scans for Total Cholesterol , HDL-cholesterol , LDL-cholesterol and triglycerides , and the Meta -Analyses of Glucose and Insulin -related traits Consortium . For SNPs significantly associated with cholesterol traits , we generated expression vectors containing the amino acid changes and measured cholesterol uptake and efflux in transfected WS fibroblasts . One SNP (rs 2230009 ) changing a valine for an isoleucine at position 114 of the WRN protein was nominally associated with cholesterol and LDL-cholesterol measurements (P-values <0 .05 ). Interestingly , a WRN cDNA expression vector bearing a valine at position 114 instead of isoleucine significantly affected cholesterol efflux in WS fibroblasts . These results implicate a functional effect of this WRN polymorphism on cholesterol metabolism .

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Diseases presenting "cholesterol" symptom

werner syndrome

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