Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Hyperuricemia and Gout: Nature Versus Nurture.

Krishnan3,  Eswar, Lessov-Schlaggar4,  Christina N., Fries2,  James F., Krasnow1,  Ruth, Swan1,  Gary E.

SRI International
Stanford Univ Medical Ctr, Palo Alto, CA
Stanford University, Palo Alto, CA
WUSTL

Background:

Hyperuricemia and gout are known to have both genetic and environmental components in their etiology. However the relative significance of each has not been well studied.

Methods:

We performed heritability analyses of hyperuricemia (SUA>7.0 mg/dL) and gout (self-reported physician diagnosis and/or use of gout medications) among the participants of a twin study. This study prospectively observed 508 twin pairs (253 monozygotic, MZ, and 261 dizygotic, DZ) over a period of 34 years. Pairwise-correlation was measured using Spearman's correlation coefficient. The relative contribution of genetic and environmental influences on phenotypic variance was estimated using standard twin methodology implemented in Mx software (PMID: 8024529).

Results:

The mean (±SD) age of the cohort was 48 (± 3) years at baseline. The baseline prevalence of gout and hyperuricemia were 3.1% and 24%, respectively. The cumulative incidence of gout did not differ between MZ and DZ twins (11.1% and 10.9%). The concordance of hyperuricemia was 56% in MZ and 31% in DZ twin pairs (p<0.001). Twin modeling showed little to no genetic influences on individual variability in gout, but substantial influence of environmental factors shared between co-twins. In contrast, individual differences in hyperuricemia were influenced by significant genetic factors with little to no evidence for an effect of shared environmental factors.

Relative contribution of genetic (A), shared environmental (C) and non-shared environment (E) influences on dichotomous measures of gout and hyperuricemia

ModelA (95% CI)C (95% CI)E (95% CI)c2dfpAICc2 diffdf diffp diff
Gout
ACE0 (0, 55.0)45.0 (0, 61.7)54.6 (35.5, 73.6)0.71030.871-5.290   
CE45.5 (26.5, 61.7)54.6 (38.3, 73.6)0.71040.950-7.2900.00011.000
AE50.5 (27.4, 69.3)49.6 (30.7, 72.7)4.38340.357-3.6173.67410.055
E10021.05050.00111.05020.34020.000
Hyperuricemia
ACE51.2 (0, 65.9)0 (0, 42.8)48.8 (34.1, 67.3)4.52530.210-1.475   
CE39.1 (24.8, 52.0)60.9 (48.0, 75.2)8.10840.0880.1083.58310.058
AE51.2 (34.1, 65.9)48.8 (34.1, 65.9)4.52540.340-3.4750.00011.000
E-10034.98550.000  24.98530.46020.000
c2-chi-square goodness of fit test; df=degrees of freedom; p-p value; AIC=Akaike information Criterion; c2 diff-chi-square difference between the fulACE model and the genetic (AE) or environmental (CE, E) submodels; df diff-degrees of freedom difference; p diff-p value associated with the chi-square goodness of fit difference

Conclusions:

Hyperuricemia, but not gout had a significant heritability component in this twin cohort. Gout variability appears to be due to environmental factors shared between cotwins. These observations need to be further studied in larger cohorts.

To cite this abstract, please use the following information:
Krishnan, Eswar, Lessov-Schlaggar, Christina N., Fries, James F., Krasnow, Ruth, Swan, Gary E.; Hyperuricemia and Gout: Nature Versus Nurture. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :877
DOI: 10.1002/art.28645

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