Genetics of variation in serum uric acid and cardiovascular risk factors in Mexican Americans.
BACKGROUND
Elevated serum uric acid is associated with several cardiovascular disease (CVD) risk factors such as hypertension, inflammation, endothelial dysfunction, insulin resistance, dyslipidemia, and obesity. However, the role of uric acid as an independent risk factor for CVD is not yet clear.


OBJECTIVE
The aim of the study was to localize quantitative trait loci regulating variation in serum uric acid and also establish the relationship between serum uric acid and other CVD risk factors in Mexican Americans (n = 848; men = 310, women = 538) participating in the San Antonio Family Heart Study.


METHODS
Quantitative genetic analysis was conducted using variance components decomposition method, implemented in the software program SOLAR.


RESULTS
Mean +/- SD of serum uric acid was 5.35 +/- 1.38 mg/dl. Univariate genetic analysis showed serum uric acid and other CVD risk markers to be significantly heritable (P < 0.005). Bivariate analysis showed significant correlation of serum uric acid with body mass index, waist circumference, waist/hip ratio, total body fat, plasma insulin, serum triglycerides, high-density lipoprotein cholesterol, C-reactive protein, and granulocyte macrophage-colony stimulating factor (P < 0.05). A genome-wide scan for detecting quantitative trait loci regulating serum uric acid variation showed a significant logarithm of odds (LOD) score of 4.72 (empirical LOD score = 4.62; P < 0.00001) on chromosome 3p26. One LOD support interval contains 25 genes, of which an interesting candidate gene is chemokine receptor 2.


CONCLUSIONS
There is a significant genetic component in the variation in serum uric acid and evidence of pleiotropy between serum uric acid and other cardiovascular risk factors.
Voruganti
V Saroja
VS
Department of Genetics, Southwest Foundation for Biomedical Research, P.O. Box 760549, San Antonio, Texas 78227, USA. svorugan@sfbrgenetics.org
Nath
Subrata D
SD
Cole
Shelley A
SA
Thameem
Farook
F
Jowett
Jeremy B
JB
Bauer
Richard
R
MacCluer
Jean W
JW
Blangero
John
J
Comuzzie
Anthony G
AG
Abboud
Hanna E
HE
Arar
Nedal H
NH
D000328:Adult; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D017058:Mexican Americans / Q000235:genetics*; D008875:Middle Aged; D040641:Quantitative Trait Loci; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood*
D014527:Uric Acid