ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1293

Identification of New and Rare Variants in ABCG2, SLC22A1 and ALDH16A1 Genes in Crystal-Proven Early-Onset Gout

Corinne Collet1, Hélène Morel1, Manon Ricquebourg1, Martine Cohen-Solal2, Jean-Louis Laplanche1, Tristan Pascart3, Thomas Bardin4, Frederic Liote5, Pascal Richette6 and Hang-Korng Ea7, 1biochemistry, Laribosiere hospital, Paris, France, 2INSERM UMR1132, Paris Diderot University, Paris, France, 3Rheumatology, Groupe Hospitalier de l'Institut Catholique de Lille, Lomme, France, 4Rheumatology, Hôpital Lariboisière, Paris, France, 5University Paris Diderot, Paris, France, 6Lariboisière Hospital, Lariboisière, University of Paris 7, Paris, France, 7INSERM UMR1132, Bioscar, University Paris Diderot, PARIS, France

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords:

Session Information

Date: Monday, October 22, 2018

Title: Metabolic and Crystal Arthropathies – Basic and Clinical Science Poster I

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

Early-onset or juvenile gout (EOG) without hypoxanthine-guanine phosphoribosyltransferase enzyme deficiency (HPRT, OMIM 300323) and not related to familial juvenile hyperuricemic nephropathy (UMOD, OMIM 300323) is a rare gout phenotype characterized by a first flare in adolescence or in young adulthood. While numerous genome wide association studies (GWAS) have been done in classical and late-onset gout, very few studies have been performed in EOG patients. Moreover, until now most genetic studies only assess association between pre-defined single nucleotide polymorphisms (SNP) and gout.

Our aim was to identify the genetic variants of clinically confirmed EOG by screening all exons of gout-associated genes with targeted Next-Generation Sequencing (NGS) approach

Methods:

Twenty-six urate crystal-proven gout patients with first flare occurring before the age of 30 years were included. Gout history, comorbidities and patient characteristics were recorded. All participants provided written informed consent to genetic analysis. After DNA extraction from total blood samples, the NGS libraries were prepared with surselectQXT (Agilent) and sequencing was performed with miseq (Illumina).

The multigene panel included 80 genes described in GWAS and genes involved in rare diseases such as HPRT and UMOD.

Results:

Twenty-six patients (24 men, 20 Caucasians, 5 Asians and 1 African) with crystal-proven gout had experienced their first flare at a mean age of 22.8 years [14-29]. Gout duration was 11.5 years [1-46] and clinical tophi observed in 9 patients. Mean age was 37.5 [24-69] years and mean body mass index 27.6 kg/m2 [20.1-40.7]. Ten patients were overweight, 5 had obesity, 1 hypertension, 0 diabetes mellitus, 7 dyslipidemia and 10 chronic kidney disease stages 2-4. Mean serum urate level was 527 µmol/L [270-803]. Amongst 26 affected patients, 7 had a molecular anomaly (26.9%). Six patients harbored one rare or novel variant in ABCG2 (three Caucasian patients), ALDH16A1 (two Caucasian patients) and SLC22A11 (one African patient). Two other patients (one Caucasian and one Asian) carried an association of variants in both ABCG2 and ALDH16A1. All variants had a Minor Allele Frequency (MAF) below 0.3% or were never described in public databases. All variant were considered as probably pathogenic according to in silico predictive algorithms. Interestingly, the well-known p.Gln141Lys SNP of ABCG2 was identified in 3 Asian patients (11.5%) at homozygous level.

Conclusion:

Our finding of very rare and novel pathogenic variants in ABCG2, ALD16H1 and SLC22A11 genes provides better insights of the molecular pathogenesis in early-onset juvenile gout. However, our results also highlight the involvement of yet undetermined genes in this population.

Disclosure: C. Collet, None; H. Morel, None; M. Ricquebourg, None; M. Cohen-Solal, None; J. L. Laplanche, None; T. Pascart, None; T. Bardin, None; F. Liote, None; P. Richette, None; H. K. Ea, None.

To cite this abstract in AMA style:

Collet C, Morel H, Ricquebourg M, Cohen-Solal M, Laplanche JL, Pascart T, Bardin T, Liote F, Richette P, Ea HK. Identification of New and Rare Variants in ABCG2, SLC22A1 and ALDH16A1 Genes in Crystal-Proven Early-Onset Gout [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/identification-of-new-and-rare-variants-in-abcg2-slc22a1-and-aldh16a1-genes-in-crystal-proven-early-onset-gout/. Accessed .

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