Background The urate transporters are one of the genetic determinants of serum uric acid concentrations. Common dysfunctional variants of ABCG2 are revealed to be a major cause of gout and hyperuricemia by decreasing urate excretion. In the present study we describe the analysis of allelic variants in the ABCG2 gene in a cohort with primary gout.

Methods The cohort consisted of 143 individuals (129 men, 14 women). Gouty arthritis was diagnosed according to the 1977 preliminary criteria of the American College of Rheumatology. Patients suffering from secondary gout were excluded. All 16 exons of ABCG2 were amplified using PCR and sequenced directly.

Results In the ABCG2 gene, 16 intronic variants were detected. In the case of c.689+1G>A, related to an individual with severe gouty phenotype, two abnormal splicing variants were identified lead to frameshift and premature stop codon introduction.¹ From the ten exon variants detected, there were eight non-synonymous: p.V12M, p.Q141K, p.R147W, p.T153M, p.F373C, p.T434M, p.S476P and p.D620N. Heterozygous p.V12M was detected in seven individuals. Heterozygous variants p.R147W, p.T153M, p.F373C, p.T434M and p.S476P were detected once, variant p.D620N twice. All these allelic variants were in silico predicted as a probably damaging and were not detected in control cohort of 150 normouricemia subjects. The p.Q141K, previously functionally characterised allelic variant with a strong effect on uric acid secretion impairment, was in cohort of gout patients presented with significantly higher minor allele frequency (MAF=0.19, 43 heterozygotes/5 homozygotes), than in population of European origin (MAF=0.09). In our cohort, the age of onset of gout had a normal distribution. Remarkably, in 75% of all individuals with early onset of gout between age 10–20 years, we detected p.Q141K (in 6 out of 8 patients). In the age group 21–30 years, p.Q141K was detected in 42% of patients (8/19), and in the age group 61–70 years, just in 29% (13/29).

Conclusions Our results show that genetic factor ABCG2 should be considered as one of the strong common risks for gout. In summary, we revealed that allelic variants of ABCG2, especially dysfunctional variant p.Q141K, have a significant effect on earlier onset of gout.

Reference 1. Stiburkova B, Miyata H, Závada J, et al. Novel dysfunctional variant in ABCG2 as a cause of severe tophaceous gout: biochemical, molecular genetics and functional analysis. Rheumatology (Oxford). 2016Jan;55(1):191-4.

This study was supported by the grants from the Czech Republic Ministry of Health AZV 15–26693A.