Copy number polymorphisms near SLC2A9 are associated with serum uric acid concentrations.
BMC Genet
; 15: 81, 2014 Jul 09.
Article
en En
| MEDLINE
| ID: mdl-25007794
ABSTRACT
BACKGROUND:
Hyperuricemia is associated with multiple diseases, including gout, cardiovascular disease, and renal disease. Serum urate is highly heritable, yet association studies of single nucleotide polymorphisms (SNPs) and serum uric acid explain a small fraction of the heritability. Whether copy number polymorphisms (CNPs) contribute to uric acid levels is unknown.RESULTS:
We assessed copy number on a genome-wide scale among 8,411 individuals of European ancestry (EA) who participated in the Atherosclerosis Risk in Communities (ARIC) study. CNPs upstream of the urate transporter SLC2A9 on chromosome 4p16.1 are associated with uric acid (χ2df2=3545, p=3.19×10-23). Effect sizes, expressed as the percentage change in uric acid per deleted copy, are most pronounced among women (3.974.935.87 [ 2.55097.5 denoting percentiles], p=4.57×10-23) and independent of previously reported SNPs in SLC2A9 as assessed by SNP and CNP regression models and the phasing SNP and CNP haplotypes (χ2df2=3190,p=7.23×10-08). Our finding is replicated in the Framingham Heart Study (FHS), where the effect size estimated from 4,089 women is comparable to ARIC in direction and magnitude (1.414.707.88, p=5.46×10-03).CONCLUSIONS:
This is the first study to characterize CNPs in ARIC and the first genome-wide analysis of CNPs and uric acid. Our findings suggests a novel, non-coding regulatory mechanism for SLC2A9-mediated modulation of serum uric acid, and detail a bioinformatic approach for assessing the contribution of CNPs to heritable traits in large population-based studies where technical sources of variation are substantial.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ácido Úrico
/
Proteínas Facilitadoras del Transporte de la Glucosa
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Variaciones en el Número de Copia de ADN
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
BMC Genet
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOTECNOLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM