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. 2007 Nov;3(11):e194.
doi: 10.1371/journal.pgen.0030194.

The GLUT9 gene is associated with serum uric acid levels in Sardinia and Chianti cohorts

Siguang Li  1 , Serena Sanna, Andrea Maschio, Fabio Busonero, Gianluca Usala, Antonella Mulas, Sandra Lai, Mariano Dei, Marco Orrù, Giuseppe Albai, Stefania Bandinelli, David Schlessinger, Edward Lakatta, Angelo Scuteri, Samer S Najjar, Jack Guralnik, Silvia Naitza, Laura Crisponi, Antonio Cao, Gonçalo Abecasis, Luigi Ferrucci, Manuela Uda, Wei-Min Chen, Ramaiah Nagaraja
Affiliations

The GLUT9 gene is associated with serum uric acid levels in Sardinia and Chianti cohorts

Siguang Li et al. PLoS Genet. 2007 Nov.

Abstract

High serum uric acid levels elevate pro-inflammatory-state gout crystal arthropathy and place individuals at high risk for cardiovascular morbidity and mortality. Genome-wide scans in the genetically isolated Sardinian population identified variants associated with serum uric acid levels as a quantitative trait. They mapped within GLUT9, a Chromosome 4 glucose transporter gene predominantly expressed in liver and kidney. SNP rs6855911 showed the strongest association (p = 1. 84 x 10(-16)), along with eight others (p = 7. 75 x 10(-16) to 6. 05 x 10(-11)). Individuals homozygous for the rare allele of rs6855911 (minor allele frequency = 0. 26) had 0. 6 mg/dl less uric acid than those homozygous for the common allele; the results were replicated in an unrelated cohort from Tuscany VSports手机版. Our results suggest that polymorphisms in GLUT9 could affect glucose metabolism and uric acid synthesis and/or renal reabsorption, influencing serum uric acid levels over a wide range of values. .

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Competing interests. The authors have declared that no competing interests exist V体育安卓版.

VSports - Figures

Figure 1
Figure 1. Genome-Wide Association Scan Results for UA Levels in Sardinian Cohort
Probability of association (plotted as −log10) according to their positions along the p to q arms of each chromosome (1 to 22 and X) for each of 362,169 SNPs that passed quality control filters. The highest p-values are at the positions of the GLUT9 and PJA2 genes, and are indicated by vertical dotted lines.
Figure 2
Figure 2. Boxplot for UA Levels Correlated with rs6855911 Genotypes in Sardinian and InCHIANTI Population Cohorts
Standard boxplots are drawn with min, 0.25 quantile; median, 0.75 quantile; and 0.75 quantile + 1.5*IQR for the levels of UA (mg/dl). To increase readability, outliers were removed from the boxplots, but they were taken into account when estimating the parameters. Sample size for each genotype class is also annotated.
Figure 3
Figure 3. Association Results and Linkage Disequilibrium Patterns in Region Surrounding the GLUT9 Gene
(A) Summary of the association between SNPs in the region and UA levels. The SNP showing strongest association (rs6855911) is highlighted. Other SNPs are colored according to their degree of disequilibrium with rs6855911, ranging from high (red), to intermediate (green), to low (blue). Transcripts in the region are indicated at the bottom of the graph, with an arrow indicating the direction of transcription. (B) Patterns of linkage disequilibrium in the region in Sardinia and in two of the HapMap populations (CEU and YRI) [25], where r 2 values are calculated according to [26] and colored as (A). The grey bar marks the region of association and facilitates comparisons between the panels.
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