Genetic influence on variation in serum uric acid in American Indians: the strong heart family study.
Hyperuricemia is associated with the metabolic syndrome, gout, renal and cardiovascular disease (CVD). American Indians have high rates of CVD and 25% of individuals in the strong heart family study (SHFS) have high serum uric acid levels. The aim of this study was to investigate the genetic determinants of serum uric acid variation in American Indian participants of the SHFS. A variance component decomposition approach (implemented in SOLAR) was used to conduct univariate genetic analyses in each of three study centers and the combined sample. Serum uric acid was adjusted for age, sex, age x sex, BMI, estimated glomerular filtration rate, alcohol intake, diabetic status and medications. Overall mean +/- SD serum uric acid for all individuals was 5.14 +/- 1.5 mg/dl. Serum uric acid was found to be significantly heritable (0.46 +/- 0.03 in all centers, and 0.39 +/- 0.07, 0.51 +/- 0.05, 0.44 +/- 0.06 in Arizona, Dakotas and Oklahoma, respectively). Multipoint linkage analysis showed significant evidence of linkage for serum uric acid on chromosome 11 in the Dakotas center [logarithm of odds score (LOD) = 3.02] and in the combined sample (LOD = 3.56) and on chromosome 1 (LOD = 3.51) in the combined sample. A strong positional candidate gene in the chromosome 11 region is solute carrier family22, member 12 (SLC22A12) that encodes a major uric acid transporter URAT1. These results show a significant genetic influence and a possible role for one or more genes on chromosomes 1 and 11 on the variation in serum uric acid in American Indian populations.
Voruganti
V Saroja
VS
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549, USA. svorugan@sfbrgenetics.org
Göring
Harald H H
HH
Mottl
Amy
A
Franceschini
Nora
N
Haack
Karin
K
Laston
Sandra
S
Almasy
Laura
L
Fabsitz
Richard R
RR
Lee
Elisa T
ET
Best
Lyle G
LG
Devereux
Richard B
RB
Howard
Barbara V
BV
MacCluer
Jean W
JW
Comuzzie
Anthony G
AG
Umans
Jason G
JG
Cole
Shelley A
SA
D001130:Arizona / Q000453:epidemiology; D002353:Carrier State; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D005190:Family; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D033461:Hyperuricemia / Q000453:epidemiology / Q000235:genetics*; D007198:Indians, North American / Q000235:genetics* / Q000706:statistics & numerical data*; D008126:Lod Score; D008297:Male; D009658:North Dakota / Q000453:epidemiology; D009825:Oklahoma / Q000453:epidemiology; D010375:Pedigree; D010641:Phenotype; D013023:South Dakota / Q000453:epidemiology; D014527:Uric Acid / Q000097:blood*
D014527:Uric Acid