Document Detail


Genome-wide search for genes affecting serum uric acid levels: the Framingham Heart Study.
MedLine Citation:
PMID:  16253630     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Serum uric acid levels are associated with hypertension, cardiovascular disease, and renal disease. Uric acid has been shown to be heritable; however, genome-wide linkage analyses have not been reported. Genome-wide multipoint variance components linkage analyses with 401 markers spaced at approximately 10 centimorgan (cM) were conducted on 1258 subjects of the Framingham Heart Study, using the average of two serum uric acid measurements obtained in examinations 1 and 2 around 1971 and 1979. Covariates in fully adjusted model included sex, age, body mass index (BMI), serum creatinine, alcohol consumption, diabetes, diuretic treatment, and triglycerides. To investigate possible pleiotropic effects between uric acid and covariates that may have a genetic component, bivariate linkage analyses of uric acid with BMI, triglycerides, and glucose were conducted at the uric acid linkage regions. The heritability of uric acid was 0.63. The highest multipoint log-of-the-odds (LOD) score was 3.3 at 50 cM on chromosome 15 for age-sex-adjusted uric acid, but decreased to 1.5 after multivariable adjustment. Additional evidence of linkage was seen on chromosomes 2 (LOD score 1.1 at 4 cM) and 8 (LOD score 1.7 at 6 cM) for multivariable-adjusted uric acid. Pleiotropic effects were only found between uric acid and glucose and BMI at chromosomes 8 and 15 linkage locations, respectively. We have identified several novel loci linked to uric acid. We found possible pleiotropic effects between uric acid and BMI and glucose. Further research is necessary to identify the genes involved in uric acid metabolism and their roles in hypertension, cardiovascular disease, and renal disease.
Authors:
Qiong Yang; Chao-Yu Guo; L Adrienne Cupples; Daniel Levy; Peter W F Wilson; Caroline S Fox
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Metabolism: clinical and experimental     Volume:  54     ISSN:  0026-0495     ISO Abbreviation:  Metab. Clin. Exp.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-10-28     Completed Date:  2005-12-28     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375267     Medline TA:  Metabolism     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1435-41     Citation Subset:  IM    
Affiliation:
Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA. qyang@bu.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Cardiovascular Diseases / genetics*,  metabolism*
Chromosomes, Human*
Chromosomes, Human, Pair 15
Chromosomes, Human, Pair 2
Chromosomes, Human, Pair 8
Cohort Studies
Female
Genome, Human*
Genomics
Humans
Linkage (Genetics)
Male
Massachusetts
Middle Aged
Uric Acid / blood*
Grant Support
ID/Acronym/Agency:
N01-HC-25195/HC/NHLBI NIH HHS
Chemical
Reg. No./Substance:
69-93-2/Uric Acid

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


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