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 .

Diseases
Validation

Diseases presenting "hypertension" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

aniridia

aromatase deficiency

cadasil

child syndrome

cohen syndrome

congenital adrenal hyperplasia

congenital diaphragmatic hernia

cushing syndrome

cystinuria

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

fabry disease

familial hypocalciuric hypercalcemia

gm1 gangliosidosis

heparin-induced thrombocytopenia

hereditary cerebral hemorrhage with amyloidosis

holt-oram syndrome

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

inclusion body myositis

kallmann syndrome

kindler syndrome

lamellar ichthyosis

lymphangioleiomyomatosis

pendred syndrome

primary effusion lymphoma

scrub typhus

severe combined immunodeficiency

sneddon syndrome

typhoid

von hippel-lindau disease

well-differentiated liposarcoma

werner syndrome

x-linked adrenoleukodystrophy

zellweger syndrome

This symptom has already been validated