This review provides an update on recent findings with regards to the genetics of hyperuricemia and gout, including recent data from genome-wide association studies (GWAS).
Five GWAS around the same time reported that genetic variants of SLC2A9/GLUT9 were associated with lower serum uric acid (SUA) levels and the effects were stronger among women (e.g. SUA level difference per copy of a minor allele, −0.46 mg/dl in women vs. −0.22 mg/dl in men). One study involving four cohorts and one meta-analysis of 14 genome-wide scans found that genetic variants of ABCG2 were associated with higher SUA concentrations and these effects were stronger among men (e.g. uric acid level difference per copy of the minor allele, 0.32 mg/dl in men vs. 0.18 mg/dl in women). Limited data indicate that these associations likely translate into those with the risk of gout. Functional determination that GLUT9 and ABCG2 can transport urate at the apical border of proximal tubules implicates them as substantial players in the renal excretion of urate. Furthermore, five novel genetic loci have been reported in the meta-analysis of 14 genome-wide scans.
Combined with their activities as urate transporters and their strong associations with serum uric acid concentrations, GLUT9 and ABCG2 appeared to be important modulators of uric acid levels and likely of the risk of gout. Together with a growing list of environmental risk factors, these genetic data add considerably to our understanding of the pathogenesis of hyperuricemia and gout.
aSection of Rheumatology and the Clinical Epidemiology Unit, USA
bClinical Epidemiology Research and Training Unit, Boston University School of Medicine, USA
cHarvard Medical School, Renal Division, Brigham and Women's Hospital, Harvard Institutes of Medicine, 4 Blackfan Circle, Boston, Renal Division, VA Boston Healthcare System, West Roxbury, Massachusetts, USA
Correspondence to Hyon K. Choi, Professor of Medicine, Section of Rheumatology and the Clinical Epidemiology Unit, 650 Albany Street, Suite 200, Boston, MA 02118, USA Tel: +1 617 638 5490; fax: +1 617-638 5239; e-mail: address: email@example.com