Common variants in SLC17A3 gene affect intra-personal variation in serum uric acid levels in longitudinal time series.
OBJECTIVE
To investigate whether intra-personal variation in serum uric acid concentration is influenced by genes that were described to be associated with serum uric acid levels in cross-sectional studies.


METHODS
The study included 92 participants from the isolated community of the Croatian island of Vis. For each participant, two uric acid concentration measurements were available, one from 2002 and one from 2003. Changes in uric acid concentration were correlated with a set of 8 genes known to affect it: PDZK1, GCKR, SLC2A9, ABCG2, LRRC16A, SLC17A3, SLC16A9, and SLC22A12.


RESULTS
Thirteen participants (14%) had uric acid concentration change greater than 130 micromol/L. Greater variability of uric acid concentration was recorded in women (coefficient of variation 49% vs 12% in men). Two SNPs belonging to SLC17A3 gene (rs9393672 and rs942379) yielded significant association with serum uric acid concentration changes in women. These two single-nucleotide polymorphisms (SNP) explained 0.2%-1.3% of variance for 2002 or 2003 uric acid measurement and 1.1%-1.8% of variance for the average value of these two measurements.


CONCLUSIONS
Repeated measurements offer a possibility to enrich the percent of explained variance and contribute to the understanding of the "missing heritability" concept. Although a number of genes have been shown to affect serum uric acid concentration, SLC17A3 seems to have a major role in determination of serum uric acid repeated measurements variation.
Polasek
Ozren
O
Andrija Stampar School of Public Health, Medical School, University of Zagreb, Rockefellerova 4, 10000 Zagreb, Croatia. opolasek@snz.hr
Jeroncić
Iris
I
Mulić
Rosanda
R
Klismanic
Zorana
Z
Pehlić
Marina
M
Zemunik
Tatijana
T
Kolcić
Ivana
I
D000368:Aged; D017523:Croatia; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D050609:Sodium-Phosphate Cotransporter Proteins, Type I / Q000235:genetics*; D014527:Uric Acid / Q000097:blood*
C493550:SLC17A3 protein, human; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D014527:Uric Acid