Background:Gout,which manifests as severe inflammation caused by excessive serum urate levels and monosodium urate deposits in the joints,is associated with multiple genomic loci in Europeans.In this exploratory work,...Background:Gout,which manifests as severe inflammation caused by excessive serum urate levels and monosodium urate deposits in the joints,is associated with multiple genomic loci in Europeans.In this exploratory work,we aimed to identify additional gene variants in Melanesian families from New Caledonia,a population in which the disease is highly prevalent.Methods:Two families from Lifou Island(New Caledonia)in which multiple members were diagnosed with gout were selected.Whole exome sequencing and/or targeted sequencing of a panel of genes involved in immunity was performed in patients and their healthy relatives.Rare variants in Melanesian populations were selected using an autosomal dominant segregation model.Results:Several variants were identified in genes not previously involved in immune diseases or hyperuricemia,several of which were not observed in control individuals from Remote Oceania.Conclusion:This work highlights new candidate susceptibility loci for gout in New Caledonians,an underrepresented population in genomic studies,and suggests that novel pathways are likely involved in gout pathogenesis.展开更多
基金supported by Strasbourg's Interdisciplinary Thematic Institute(ITI)for Precision Medicine,TRANSPLANTEX NG,as part of the ITI 2021-2028 program of the University of Strasbourg,CNRS and INSERM,funded by IdEx Unistra(ANR-10-IDEX-0002)SFRI-STRAT'US(ANR-20-SFRI-0012)+2 种基金the INSERM UMR_S 1109,the University of Strasbourg(IDEX UNISTRA)the European regional development fund(European Union)INTERREG V program(project PERSONALIS)the MSD-Avenir grant AUTOGEN.RC is supported by the“Association Robert Debrépour la Recherche Médicale.”。
文摘Background:Gout,which manifests as severe inflammation caused by excessive serum urate levels and monosodium urate deposits in the joints,is associated with multiple genomic loci in Europeans.In this exploratory work,we aimed to identify additional gene variants in Melanesian families from New Caledonia,a population in which the disease is highly prevalent.Methods:Two families from Lifou Island(New Caledonia)in which multiple members were diagnosed with gout were selected.Whole exome sequencing and/or targeted sequencing of a panel of genes involved in immunity was performed in patients and their healthy relatives.Rare variants in Melanesian populations were selected using an autosomal dominant segregation model.Results:Several variants were identified in genes not previously involved in immune diseases or hyperuricemia,several of which were not observed in control individuals from Remote Oceania.Conclusion:This work highlights new candidate susceptibility loci for gout in New Caledonians,an underrepresented population in genomic studies,and suggests that novel pathways are likely involved in gout pathogenesis.
