Novel genetic loci in early-onset gout derived from whole genome sequencing of an adolescent gout cohort.

OBJECTIVE: Mechanisms underlying the adolescent-onset and early-onset gout are unclear. This study aimed to discover variants associated with early-onset gout. METHODS: We conducted whole genome sequencing in a discovery adolescent-onset gout cohort of 905 individuals (gout onset 12-19 years) to discover common and low frequency SNVs associated with gout. Candidate common SNVs were genotyped in an early-onset gout cohort of 2834 individuals (gout onset ≤ 30 years old) and meta-analysis was performed with the discovery and replication cohorts to identify loci associated with early-onset gout. Transcriptome and epigenomic analyses, RT-qPCR and RNA-seq in human peripheral blood leukocytes, and knock-down experiments in human THP-1 macrophage cells investigated the regulation and function of candidate gene RCOR1. RESULTS: In addition to ABCG2, a urate transporter previously linked to pediatric-onset and early-onset gout, we identified two novel loci (Pmeta < 5.0 × 10-8): rs12887440 (RCOR1) and rs35213808 (FSTL5-MIR4454). Additionally, we found associations at ABCG2 and SLC22A12 that were driven by low frequency SNVs. SNVs in RCOR1 were linked to elevated blood leukocyte mRNA levels. THP-1 macrophage culture studies revealed the potential of decreased RCOR1 to suppress gouty inflammation. CONCLUSION: This is the first comprehensive genetic characterization of adolescent-onset gout. The identified risk loci of early-onset gout mediate inflammatory responsiveness to crystals that could mediate gouty arthritis. This study will contribute to risk prediction and therapeutic interventions to prevent adolescent-onset gout.

Clinical characteristics of adolescent-onset gout in Chinese: A hospital-based cross-sectional study.

OBJECTIVE: Adolescent-onset gout has a greater impact on the lives and health of patients than adult-onset gout. However, there is a relative lack of clinical information on adolescent-onset gout. Hence, we analyzed a Chinese cohort. METHODS: We studied clinical features of 9,003 Chinese patients. Gout onset age of 12 - 19 years is defined as adolescent-onset group (AG), 20 - 40 years as early-onset group (EG), and 41 - 64 years as late-onset group (LG). Multivariable regression analysis evaluated factors associated with recurrent flares, serum urate (SU) levels, and underexcretion type in AG. RESULTS: Compared with EG and LG, the AG had higher SU levels [AG: 9.5 (2.2) mg/dL, EG: 8.6 (2.1) mg/dL, LG: 7.73 (2.0) mg/dL, P < 0.001], higher percentage of positive family history of gout (AG: 41.8 %, EG: 29.6 %, LG: 24.6 %, P < 0.001), underexcretion type (AG: 62.4 %, EG: 62.5 %, LG: 58.8 %, P = 0.04), recurrent flares (AG: 78.1 %, EG: 70.3 %, LG: 68.9 %, P = 0.01). Urate-lowering therapy (ULT) initiated [OR 6.58 (95 % CI 1.35 - 32.00)] and hypercholesterolemia [OR 4.16 (95 % CI 1.28 - 13.53)] were associated with recurrent flares. eGFR was identified to be a significant variable of increasing SU levels [beta -0.24 (95 % CI -0.04 to -0.01)]. Hypertriglyceridemia [OR 0.35 (95 % CI 0.17 - 0.71)] was related to underexcretion type. CONCLUSION: Adolescent-onset gout patients had clinically distinctive features with higher SU levels, BMI, positive gout family history, underexcretion type and recurrent flares. These specific populations were less likely to achieve ULT target, requiring more clinical attention.

[Genetic polymorphism of bluegrass cultivars detected by RAPDs].

Kentucky bluegrass (Poa pratensis L.) is a hardy, persistent forage and turf grass adapted to a wide range of soils and climates. Its ever-increasing adoption in highly cared-for sports fields has attracted the attention of many seed companies. However in the past, the breeding of elite varieties was often hampered by the extreme complexity of the genome. The polymorphism is important for broading the genetic basis and may be exploited for application of heterosis. The genetic relationship of 16 bluegrass cultivars, including 15 accessions Kentucky bluegrass cultivars and 1 entries Canada bluegrass (Poa compressa L.) cultivar from different breeding company were analyzed using 25 RAPD markers. 25 RAPD primers generated 218 bands, of which 196 bands (89.91%) were polymorphism. It showed that the Canada Bluegrass was separated from other Kentucky Bluegrass and genetic polymorphism in the Kentucky Bluegrass cultivars was low, the genetic similarity among the cultivars fell between 66%-98%. Dendrogram obtained using these molecular markers were partly in agreement with their separated morphologic character. Cultivars from the same company were not clustered in one group.