Sex and age interaction with genetic association of atherogenic uric acid concentrations.
BACKGROUND
High serum uric acid levels are associated with gout, atherosclerosis and cardiovascular disease. Three genes (SLC2A9, ABCG2, and SLC17A3) were reported to be involved in the regulation of uric acid levels.


METHODS



METHODS
SNPs rs2231142 (ABCG2) and rs1165205 (SLC17A3) were genotyped in three cohorts (n=4492) and combined with previously genotyped SNPs within SLC2A9 (rs6855911, rs7442295, rs6449213, rs12510549).


RESULTS
Each copy of the minor allele decreased uric acid levels by 0.30-0.38 mg/dL for SLC2A9 (p values: 10(-20)-10(-36)) and increased levels by 0.34 mg/dL for ABCG2 (p=1.1x10(-16)). SLC17A3 influenced uric acid levels only modestly. Together the SNPs showed graded associations with uric acid levels of 0.111 mg/dL per risk allele (p=3.8x10(-42)). In addition, we observed a sex-specific interaction of age with the association of SLC2A9 SNPs with uric acid levels, where increasing age strengthened the association of SNPs in women and decreased the association in men.


CONCLUSIONS
Genetic variants within SLC2A9,ABCG2 and SLC17A3 show highly significant associations with uric acid levels, and for SNPs within SLC2A9 this association is strongly modified by age and sex.
Brandstätter
Anita
A
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schöpfstr. 41, A-6020 Innsbruck, Austria.
Lamina
Claudia
C
Kiechl
Stefan
S
Hunt
Steven C
SC
Coassin
Stefan
S
Paulweber
Bernhard
B
Kramer
Felix
F
Summerer
Monika
M
Willeit
Johann
J
Kedenko
Lyudmyla
L
Adams
Ted D
TD
Kronenberg
Florian
F
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000367:Age Factors; D000368:Aged; D050197:Atherosclerosis / Q000453:epidemiology* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D006073:Gout / Q000453:epidemiology* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D050609:Sodium-Phosphate Cotransporter Proteins, Type I / Q000235:genetics; D014527:Uric Acid / Q000378:metabolism*
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D051246:Glucose Transport Proteins, Facilitative; D009363:Neoplasm Proteins; C493550:SLC17A3 protein, human; C411811:SLC2A9 protein, human; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D014527:Uric Acid