Susceptibility genes of hyperuricemia and gout

Nian, Yueli; You, Chongge

doi:10.1186/s41065-022-00243-y

Cited by 17 publications

(5 citation statements)

References 118 publications

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“…We further replicated the previously reported sex differences for the lead variants near SLC2A9, ABCG2 , and ALDH16A1 6,37,38 . ALDH16A1 rs150414818 (missense, Pro476Arg) has been found to disrupt the interaction between ALDH16A1 and HPRT1 ( hypoxanthine phosphoribosyltransferase 1 ) and thus potentially lead to urate overproduction via the purine salvage pathway 39,40 . HPRT1 is located on the X-chromosome and may thus contribute to explaining the sex differences in the effect sizes observed for ALDH16A1 variants.…”

Section: Discussionmentioning

confidence: 99%

Exploring metabolic changes in gout – Insights from a genetic study

Salo,

Kettunen,

Sliz

2024

Preprint

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Gout is the most common inflammatory joint disease caused by the crystallization of urate inside the joints. Patients with gout typically have abnormal blood lipid and sugar levels, which are associated with cardiovascular diseases. However, the relationship between gout and metabolic changes is unclear. Our goal was two-fold: to identify new gout risk factors using genome-wide association analysis and subsequently to investigate the effects of the identified risk alleles on metabolic measures in the bloodstream. We performed a genome-wide meta-analysis for gout in the FinnGen project, the Estonian Biobank, and the UK Biobank, encompassing a total of 992,583 individuals, including 17,972 gout cases. Given that gout is commonly recognized as a disease affecting the elderly, and males specifically, we further explored age- and sex-stratified genetic associations in FinnGen (10,885 cases and 366,392 controls). Finally, we determined the metabolomic consequences of the gout risk-increasing alleles using data from a large metabolomics GWAS. In the meta-analysis, we observed 32 genome-wide significant (P<5×10−8) loci, one of which was novel. In the age- and sex-stratified analyses, we additionally identified one novel gout-associated locus in the male subgroup. The metabolomic findings suggested that the majority of the gout risk alleles primarily affected urate concentration in the bloodstream but not the concentrations of lipids and other metabolites. Therefore, it appears that the associations between gout and metabolic factors at the population level are likely explained by shared lifestyle risk factors. In conclusion, our study sheds new light on the genetic architecture of gout and adds to the growing body of evidence supporting the role of urate, but not other metabolic measures, including lipoprotein lipids and glucose, as a key risk factor for developing gout.

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Section: Discussionmentioning

confidence: 99%

Exploring metabolic changes in gout – Insights from a genetic study

Salo,

Kettunen,

Sliz

2024

Preprint

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“…Considering the epidemiology of gout, this case was unusual because it affected a woman at a younger age. Recently, several studies have shown that gene alterations may play a significant role in hyperuricemia and gout development; however, the mechanism or genetic etiology has not been fully confirmed ( 33 ). The association of FAM111A variants with hyperuricemia remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Case report: Late middle-aged features of FAM111A variant, Kenny–Caffey syndrome type 2-suggestive symptoms during a long follow-up

Ohmachi

Urai²,

Bando³

et al. 2023

Front. Endocrinol.

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Kenny–Caffey syndrome type 2 (KCS2) is an extremely rare skeletal disorder involving hypoparathyroidism and short stature. It has an autosomal dominant pattern of inheritance and is caused by variants in the FAM111 trypsin-like peptidase A (FAM111A) gene. This disease is often difficult to diagnose due to a wide range of more common diseases manifesting hypoparathyroidism and short stature. Herein, we present the case of a 56-year-old female patient with idiopathic hypoparathyroidism and a short stature. The patient was treated for these conditions during childhood. Upon re-evaluating the etiology of KCS2, we suspected that the patient had the disorder because of clinical manifestations, such as cortical thickening and medullary stenosis of the bones, and lack of intellectual abnormalities. Genetic testing identified a heterozygous missense variant in the FAM111A gene (p.R569H). Interestingly, the patient also had bilateral sensorineural hearing loss and vestibular dysfunction, which have been rarely described in previous reports of pediatric cases. In KCS2, inner ear dysfunction due to Eustachian tube dysfunction may progress in middle age or later. However, this disease is now being reported in younger patients. Nevertheless, our case may be instructive of how such cases emerge chronically after middle age. Herein, we also provide a literature review of KCS2.

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“…2 HUA is defined by a serum uric acid (SUA) concentration exceeding 7.0 mg dL −1 in men or 6.0 mg dL −1 in women. 3,4 Persistent elevation of SUA beyond physiological saturation fosters the formation of sodium urate (MSU) crystals, which can deposit in joints, connective tissue, and kidneys, leading to gouty arthritis and kidney stones. 5 Moreover, prolonged uncontrolled elevation in uric acid levels heightens the risk of hypertension and diabetes.…”

Section: Introductionmentioning

confidence: 99%