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Genomic Influences on Hyperuricemia and Gout
1Department of Biochemistry, University of Otago, 710 Cumberland Street, Dunedin 9054, New Zealand.
Rheumatic Diseases Clinics of North America
|July 17, 2017
Summary
Genome-wide association studies identified genetic factors influencing urate levels and gout risk. The ABCG2 Q141K variant is a likely cause, and other urate transporter genes are implicated in gout development.
Area of Science:
- Genetics
- Metabolic Disorders
- Rheumatology
Background:
- Genome-wide association studies (GWAS) have identified numerous genetic loci linked to serum urate concentrations.
- These loci also influence the risk of developing gout, a metabolic condition characterized by high urate levels.
- Identifying the specific causal genes within these loci remains a significant challenge.
Purpose of the Study:
- To investigate the genetic underpinnings of urate concentrations and their association with gout risk.
- To identify causal genes at GWAS loci influencing urate levels.
- To explore the genetic control of the progression from hyperuricemia to gout.
Main Methods:
- Analysis of genome-wide association study (GWAS) data for urate concentrations and gout.
- Evaluation of specific genetic variants, such as the ABCG2 Q141K variant.
- Review of existing literature on urate transporter genes and gout-associated loci.
Main Results:
- Nearly 30 loci associated with urate concentrations and gout risk have been identified through GWAS.
- The ABCG2 Q141K variant is strongly implicated as a causal factor, affecting ABCG2 protein localization.
- Three additional GWAS loci contain uric acid transporter genes, suggesting their causal role in urate homeostasis and gout.
- The genetic basis for gout progression from hyperuricemia is less understood, with limited GWAS data available.
Conclusions:
- GWAS have significantly advanced the understanding of genetic factors influencing urate levels and gout susceptibility.
- Specific variants like ABCG2 Q141K and urate transporter genes are key targets for understanding gout pathogenesis.
- Further research, including larger GWAS, is needed to elucidate the genetic control of gout progression.
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